Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential assembly of stable bardet-biedl syndrome protein complex, the BBSome

Qihong Zhang; Dahai Yu; Seongjin Seo; Edwin M Stone; Val C Sheffield

doi:10.1074/jbc.M112.341487

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Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential assembly of stable bardet-biedl syndrome protein complex, the BBSome

Journal article

Open access

Peer reviewed

Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential assembly of stable bardet-biedl syndrome protein complex, the BBSome

Qihong Zhang, Dahai Yu, Seongjin Seo, Edwin M Stone and Val C Sheffield

The Journal of biological chemistry, Vol.287(24), pp.20625-20635

06/08/2012

DOI: 10.1074/jbc.M112.341487

PMCID: PMC3370246

PMID: 22500027

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Abstract

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.

Cell Line

Bardet-Biedl Syndrome - metabolism

Microtubule-Associated Proteins - genetics

Microtubule-Associated Proteins - metabolism

Humans

Male

Multiprotein Complexes - genetics

Mice, Knockout

Group II Chaperonins - genetics

Multiprotein Complexes - metabolism

Point Mutation

Group II Chaperonins - metabolism

Animals

Bardet-Biedl Syndrome - genetics

Female

Mice

Details

Title: Subtitle: Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential assembly of stable bardet-biedl syndrome protein complex, the BBSome
Creators: Qihong Zhang - Department of Pediatrics, Division of Medical Genetics and Howard Hughes Medical Institute, University of Iowa, Iowa City 52242, USA
Dahai Yu
Seongjin Seo
Edwin M Stone
Val C Sheffield
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.287(24), pp.20625-20635
DOI: 10.1074/jbc.M112.341487
PMID: 22500027
PMCID: PMC3370246
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: R01 NS083543 / NINDS NIH HHS R01EY017168 / NEI NIH HHS R01EY110298 / NEI NIH HHS Howard Hughes Medical Institute R01 EY017168 / NEI NIH HHS
Language: English
Date published: 06/08/2012
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983979962402771

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