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<meta name="description" content="The pleiotropic features of obesity, retinal degeneration, polydactyly, kidney abnormalities, cognitive impairment, hypertension, and diabetes found in Bardet-Biedl syndrome (BBS) make this disorder an important model disorder for identifying molecular mechanisms involved in common human diseases. T …"><meta name="keywords" content="pmid:22500027, PMC3370246, doi:10.1074/jbc.M112.341487, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov&#x27;t, Qihong Zhang, Dahai Yu, Val C Sheffield, Animals, Bardet-Biedl Syndrome / genetics, Bardet-Biedl Syndrome / metabolism, Cell Line, Female, Group II Chaperonins / genetics, Group II Chaperonins / metabolism*, Humans, Male, Mice, Mice, Knockout, Microtubule-Associated Proteins / genetics, Microtubule-Associated Proteins / metabolism*, Multiprotein Complexes / genetics, Multiprotein Complexes / metabolism*, Point Mutation, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential assembly of stable bardet-biedl syndrome protein complex, the BBSome - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/22500027/"><meta property="og:description" content="The pleiotropic features of obesity, retinal degeneration, polydactyly, kidney abnormalities, cognitive impairment, hypertension, and diabetes found in Bardet-Biedl syndrome (BBS) make this disorder an important model disorder for identifying molecular mechanisms involved in common human diseases. T …"><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential assembly of stable bardet-biedl syndrome protein complex, the BBSome - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/22500027/"><meta name="twitter:description" content="The pleiotropic features of obesity, retinal degeneration, polydactyly, kidney abnormalities, cognitive impairment, hypertension, and diabetes found in Bardet-Biedl syndrome (BBS) make this disorder an important model disorder for identifying molecular mechanisms involved in common human diseases. T …"><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg">
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<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="kXyRIiYylPWWg0YgCFdLcZygB6U4DNcfBKiWl8rUVqJqar46fYQNG74U9aCgwoKz">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="kXyRIiYylPWWg0YgCFdLcZygB6U4DNcfBKiWl8rUVqJqar46fYQNG74U9aCgwoKz">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="kXyRIiYylPWWg0YgCFdLcZygB6U4DNcfBKiWl8rUVqJqar46fYQNG74U9aCgwoKz">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="kXyRIiYylPWWg0YgCFdLcZygB6U4DNcfBKiWl8rUVqJqar46fYQNG74U9aCgwoKz">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="kXyRIiYylPWWg0YgCFdLcZygB6U4DNcfBKiWl8rUVqJqar46fYQNG74U9aCgwoKz">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="22500027">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)49933-8"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3048&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=22500027&amp;db=pubmed&amp;nlmid=2985121R"
title="See full text options at Elsevier Science"
data-ga-category="full_text"
data-ga-action="Elsevier Science"
data-ga-label="22500027"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-elsevieroa.png" alt="Elsevier Science full text link"><span class="text">
Elsevier Science
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/22500027/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=22500027&amp;db=pubmed&amp;nlmid=2985121R"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="22500027"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/22500027/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/22500027/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="22500027" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F22500027%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="kXyRIiYylPWWg0YgCFdLcZygB6U4DNcfBKiWl8rUVqJqar46fYQNG74U9aCgwoKz"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="collections_button"
data-ga-action="create_collection"
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Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential assembly of stable bardet-biedl syndrome protein complex, the BBSome
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The pleiotropic features of obesity, retinal degeneration, polydactyly, kidney abnormalities, cognitive impairment, hypertension, and diabetes found in Bardet-Biedl syndrome (BBS) make this disorder an important model disorder for identifying molecular mechanisms involved in common human diseases. To date, 16 BBS genes have been reported, seven of which (BBS1, 2, 4, 5, 7, 8, and 9) code for proteins that form a complex known as the BBSome. The function of the BBSome involves ciliary membrane biogenesis. Three additional BBS genes (BBS6, BBS10, and BBS12) have homology to type II chaperonins and interact with CCT/TRiC proteins and BBS7 to form a complex termed the BBS-chaperonin complex. This complex is required for BBSome assembly. Little is known about the process and the regulation of BBSome formation. We utilized point mutations and null alleles of BBS proteins to disrupt assembly of the BBSome leading to the accumulation of BBSome assembly intermediates. By characterizing BBSome assembly intermediates, we show that the BBS-chaperonin complex plays a role in BBS7 stability. BBS7 interacts with BBS2 and becomes part of a BBS7-BBS2-BBS9 assembly intermediate referred to as the BBSome core complex because it forms the core of the BBSome. BBS1, BBS5, BBS8, and finally BBS4 are added to the BBSome core to form the complete BBSome.
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<div class="figures" id="figures">
<h2 class="title">
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</h2>
<div class="figures-list" id="slides-container"
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<figure class="figure-item "
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itemprop="associatedMedia"
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data-label-slug="figure-1">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271e/3370246/028b04b5daea/zbc0251210970001.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-0"
role="button"
data-image-width="683"
data-image-height="501"
data-image-alt="FIGURE 1."
data-pmc-id="PMC3370246"
data-figure-id="F1">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-0"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271e/3370246/a25b18b8c90c/zbc0251210970001.gif"
alt="FIGURE 1." />
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<div class="caption-wrap">
<strong class="figure-label">
<p> FIGURE 1. </p>
</strong>
<div class="figure-caption-contents"><b> BBS2, BBS7, and BBS9 form… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> FIGURE 1. </p>
</strong>
<div class="figure-caption-contents"><b> BBS2, BBS7, and BBS9 form the BBSome core complex. </b> <i> A </i> , FLAG-tagged BBS7…</div>
</div>
<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
FIGURE 1.
</strong>
<div class="figure-caption-contents"><b>BBS2, BBS7, and BBS9 form the BBSome core complex.</b>
<i>A</i>, FLAG-tagged BBS7 containing a point mutation (T211I) and WT BBS7 were transfected into 293T cells. Both WT and mutant BBS7 were pulled down by FLAG beads. The existence of other endogenous BBSome subunits is detected by Western blot. <i>B</i>, the absence of BBS2 affects the interaction of BBS7 with BBS1, whereas the loss of BBS1 does not affect the interaction of BBS7 with BBS2. <i>C</i>, FLAG-tagged BBS5, BBS8, BBS9, and BBIP10 were transfected into 293T cells. Tagged proteins were immunoprecipitated (<i>IP</i>) by FLAG beads, and the existence of other endogenous BBSome subunits was detected by Western blot. <i>D</i>, BBS9 RNAi was used to knock down endogenous BBS9 expression in a stable cell line expressing FLAG-BBS2. The BBSome was immunoprecipitated by FLAG beads, and the existence of endogenous BBSome subunits was detected by Western blot.</div>
</figcaption>
</figure>
<figure class="figure-item "
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data-label-slug="figure-2">
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271e/3370246/a7857a4d114e/zbc0251210970002.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-1"
role="button"
data-image-width="683"
data-image-height="504"
data-image-alt="FIGURE 2."
data-pmc-id="PMC3370246"
data-figure-id="F2">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-1"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271e/3370246/0b9c725bd24b/zbc0251210970002.gif"
alt="FIGURE 2." />
</a>
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<strong class="figure-label">
<p> FIGURE 2. </p>
</strong>
<div class="figure-caption-contents"><b> BBS1 is incorporated into the… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> FIGURE 2. </p>
</strong>
<div class="figure-caption-contents"><b> BBS1 is incorporated into the BBSome before BBS4. </b> <i> A </i> , Western blots of…</div>
</div>
<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
FIGURE 2.
</strong>
<div class="figure-caption-contents"><b>BBS1 is incorporated into the BBSome before BBS4.</b>
<i>A</i>, Western blots of protein lysates from WT and <i>Bbs1<sup>M390R/M390R</sup></i> mice demonstrate that the absence of BBS1 does not affect other BBSome subunits protein levels, whereas BBS1 protein levels are greatly decreased in samples from <i>Bbs1<sup>M390R/M390R</sup></i> mice as indicated by the <i>arrow</i>. This antibody also recognizes several additional bands that do not change in intensity when compared between WT and <i>Bbs1<sup>M390R/M390R</sup></i> mice, indicating that these bands are nonspecific. <i>B</i>, sucrose gradient analysis of BBSome formation in <i>Bbs1<sup>M390R</sup></i> testes demonstrates that most BBS4 is dissociated from the subcomplex consisting of BBS2, BBS5, BBS7, BBS8, and BBS9. <i>C</i>, immunoprecipitation (<i>IP</i>) using antibody against BBS2 from testes protein lysates shows that BBS4 is dissociated from the subcomplex in the absence of BBS1. These results are similar to those shown by sucrose gradient analysis. <i>D</i>, reciprocal immunoprecipitation from transfected 293T cells demonstrates that BBS4 dissociation from BBS1<sup>M390R</sup> is due to decreased interaction between BBS1<sup>M390R</sup> and BBS4 compared with WT BBS1. <i>E</i>, diagram showing the sequential order of BBS1 and BBS4 incorporation into the BBSome.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
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data-slide-index="2"
data-label-slug="figure-3">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271e/3370246/d1e4c3520f76/zbc0251210970003.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-2"
role="button"
data-image-width="683"
data-image-height="460"
data-image-alt="FIGURE 3."
data-pmc-id="PMC3370246"
data-figure-id="F3">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-2"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271e/3370246/4282cebcc525/zbc0251210970003.gif"
alt="FIGURE 3." />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="683">
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<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> FIGURE 3. </p>
</strong>
<div class="figure-caption-contents"><b> BBS4 is likely the last… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> FIGURE 3. </p>
</strong>
<div class="figure-caption-contents"><b> BBS4 is likely the last subunit to incorporate into the BBSome. </b> <i> A </i> ,…</div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
FIGURE 3.
</strong>
<div class="figure-caption-contents"><b>BBS4 is likely the last subunit to incorporate into the BBSome.</b>
<i>A</i>, sucrose gradient analysis of BBSome formation in <i>Bbs4</i><sup>/</sup> testes lysates demonstrates that all other BBSome subunits can still form a complex in the absence of BBS4. <i>B</i>, immunoprecipitation using anti-BBS2 antibody from testes protein lysates indicates that BBS4 is the last subunit to incorporate into the BBSome. <i>C</i>, diagram showing the sequential order of BBS components incorporation into the BBSome.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="3"
data-label-slug="figure-4">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271e/3370246/0fc0405a425c/zbc0251210970004.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-3"
role="button"
data-image-width="492"
data-image-height="403"
data-image-alt="FIGURE 4."
data-pmc-id="PMC3370246"
data-figure-id="F4">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-3"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271e/3370246/c3b175fe41a0/zbc0251210970004.gif"
alt="FIGURE 4." />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="492">
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<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> FIGURE 4. </p>
</strong>
<div class="figure-caption-contents"><b> BBS4-PCM1 interaction is required for… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> FIGURE 4. </p>
</strong>
<div class="figure-caption-contents"><b> BBS4-PCM1 interaction is required for the BBSome to localize to centrosome/pericentriolar satellite. </b> <i> A… </i></div>
</div>
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
FIGURE 4.
</strong>
<div class="figure-caption-contents"><b>BBS4-PCM1 interaction is required for the BBSome to localize to centrosome/pericentriolar satellite.</b>
<i>A</i>, BBS4 point mutations (G277E and R295P) disrupt the interaction between BBS4 and the C terminus of PCM1. GFP-tagged BBS4 (WT or mutants) and HA-tagged PCM1 C terminus were co-transfected into 293T cells, and co-immunoprecipitation (<i>IP</i>) was performed using antibody against HA and GFP. <i>B</i>, BBS4 point mutations (G277E and R295P) disrupt centrosome/pericentriolar satellite localization of BBS4. Shown is immunofluorescent staining of GFP-BBS4 (WT and mutants) in transfected RPE1 cells. γ-Tubulin (<i>red</i>) is used as a centrosomal marker. <i>C</i>, kidney primary cells were transfected with GFP-BBS4, and transfected cells were co-stained with γ-tubulin. The <i>bar</i> represents 10 μm.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="4"
data-label-slug="figure-5">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271e/3370246/7a6524fa2215/zbc0251210970005.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-4"
role="button"
data-image-width="633"
data-image-height="655"
data-image-alt="FIGURE 5."
data-pmc-id="PMC3370246"
data-figure-id="F5">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-4"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271e/3370246/13e5df4065ce/zbc0251210970005.gif"
alt="FIGURE 5." />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="633">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="655">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> FIGURE 5. </p>
</strong>
<div class="figure-caption-contents"><b> BBS10 is required for the… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> FIGURE 5. </p>
</strong>
<div class="figure-caption-contents"><b> BBS10 is required for the interaction of BBS6-BBS12-BBS7 with the CCT/TRiC proteins to… </b></div>
</div>
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
FIGURE 5.
</strong>
<div class="figure-caption-contents"><b>BBS10 is required for the interaction of BBS6-BBS12-BBS7 with the CCT/TRiC proteins to form the BBS-chaperonin complex.</b>
<i>A</i>, BBS10 RNAi is used to knock down the expression of BBS10 in 293T cells expressing FLAG-BBS6, which was used to pull down the BBS-chaperonin complex. Antibodies against BBS7 and the CCT/TRiC proteins were used to detect the existence of these proteins in the complex. <i>B</i>, overexpression of BBS10 facilitates the association of BBS6 with the CCT/TRiC proteins. FLAG-BBS10 was co-transfected with empty vector or Myc-BBS6, and Myc antibody was used to pull down the BBS-chaperonin complex. Antibodies against BBS7, TCPα, and TCPβ (two subunits of the CCT/TRiC proteins) were used to detect these proteins in the complex. <i>IP</i>, immunoprecipitation.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="5"
data-label-slug="figure-6">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271e/3370246/33157c97f5e0/zbc0251210970006.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-5"
role="button"
data-image-width="700"
data-image-height="589"
data-image-alt="FIGURE 6."
data-pmc-id="PMC3370246"
data-figure-id="F6">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-5"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271e/3370246/c0410d2ca631/zbc0251210970006.gif"
alt="FIGURE 6." />
</a>
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<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> FIGURE 6. </p>
</strong>
<div class="figure-caption-contents"><b> The release of BBS7 from… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> FIGURE 6. </p>
</strong>
<div class="figure-caption-contents"><b> The release of BBS7 from the BBS-chaperonin complex is coordinated with BBSome core… </b></div>
</div>
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
FIGURE 6.
</strong>
<div class="figure-caption-contents"><b>The release of BBS7 from the BBS-chaperonin complex is coordinated with BBSome core complex formation.</b>
<i>A</i>, FLAG-BBS6 was overexpressed in 239T cells to trap BBSome intermediates. We pulled down BBS6 using FLAG beads and detected endogenous BBSome subunits by Western blot. FLAG-BBS5 was used as a positive control, and FLAG-GFP was used as a negative control. <i>B</i>, individual BBSome subunits were overexpressed in 293T cells and were used to determine specific associations with the CCT/TRiC proteins. Only BBS7 and BBS2 can associate with CCT/TRiC proteins. FLAG-VHL was used as a positive control. FLAG-GFP and FLAG-BBS3 were used as negative controls. <i>IP</i>, immunoprecipitation.</div>
</figcaption>
</figure>
<figure class="figure-item tail"
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271e/3370246/88a2e0f5c4b5/zbc0251210970007.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-6"
role="button"
data-image-width="492"
data-image-height="367"
data-image-alt="FIGURE 7."
data-pmc-id="PMC3370246"
data-figure-id="F7">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-6"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271e/3370246/54eb739e58b6/zbc0251210970007.gif"
alt="FIGURE 7." />
</a>
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<div class="caption-wrap">
<strong class="figure-label">
<p> FIGURE 7. </p>
</strong>
<div class="figure-caption-contents"><b> BBS2 is ubiquitinated and degraded… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> FIGURE 7. </p>
</strong>
<div class="figure-caption-contents"><b> BBS2 is ubiquitinated and degraded by the proteasome. </b> <i> A </i> , the stability of…</div>
</div>
<figcaption id="figure-caption-6" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
FIGURE 7.
</strong>
<div class="figure-caption-contents"><b>BBS2 is ubiquitinated and degraded by the proteasome.</b>
<i>A</i>, the stability of BBS2 is dependent on the BBSome core complex, as well as the BBS-chaperonin complex. Proteins from BBS knock-out mouse tissue (testis) or from RNAi-treated cell lysates were separated by SDS-PAGE. Anti-BBS2 antibody was used to detect BBS2 protein levels. <i>B</i>, BBS2 is sensitive to protease treatment. Primary cells from WT and <i>Bbs6</i><sup>/</sup> kidney were infected with adenovirus expressing FLAG-BBS2. Equal amounts of total proteins were mixed with protease thermolysin at 4 °C for the indicated time. Compared with WT cells, BBS2 degrades faster in <i>Bbs6</i><sup>/</sup> cells, suggesting that BBS2 is not stable in the absence of BBS6. <i>C</i>, 293T cells and FLAG-BBS2 stable-expressing cells were treated with the proteasome inhibitor MG132. BBS2 was immunoprecipitated (<i>IP</i>) by FLAG beads or anti-BBS2 antibody, and ubiquitinated BBS2 was detected by anti-ubiquitin antibody. <i>D</i>, HA-ubiquitin was transfected into 293T cells, and endogenous BBS2 was immunoprecipitated by anti-BBS2 antibody. Ubiquitinated BBS2 was detected by anti-HA antibody or anti-ubiquitin antibody. <i>E</i>, 293T cells were treated with 50 μg/ml of cycloheximide (<i>Chx</i>) with or without 20 μ<sc>m</sc> proteasome inhibitor MG132 or MG115 for 8 h. Endogenous BBS2 in the cell lysates was detected by anti-BBS2 antibody.</div>
</figcaption>
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271e/3370246/eb49babc9cd7/zbc0251210970008.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-7"
role="button"
data-image-width="683"
data-image-height="479"
data-image-alt="FIGURE 8."
data-pmc-id="PMC3370246"
data-figure-id="F8">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-7"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271e/3370246/064e586f1ad0/zbc0251210970008.gif"
alt="FIGURE 8." />
</a>
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<div class="caption-wrap">
<strong class="figure-label">
<p> FIGURE 8. </p>
</strong>
<div class="figure-caption-contents"><b> Intrinsic protein-protein interactions and chaperonin… </b></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> FIGURE 8. </p>
</strong>
<div class="figure-caption-contents"><b> Intrinsic protein-protein interactions and chaperonin mediated sequential assembly of the BBSome. </b> Shown are…</div>
</div>
<figcaption id="figure-caption-7" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
FIGURE 8.
</strong>
<div class="figure-caption-contents"><b>Intrinsic protein-protein interactions and chaperonin mediated sequential assembly of the BBSome.</b> Shown are diagrams of our current model for BBSome assembly. BBS7 is stabilized by the BBS-chaperonin complex (BBS6-BBS12-BBS7-CCT) and makes a transition to the BBSome core complex (BBS7-BBS2-BBS9). This transition requires BBS10. The intrinsic protein-protein interactions guide the incorporation of BBS1, BBS5, and BBS8. BBS4 requires BBS1 to incorporate into the complex and is the last subunit to be added to the complex.</div>
</figcaption>
</figure>
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