The Molecular Architecture of Native BBSome Obtained by an Integrated Structural Approach.


Journal

Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697

Informations de publication

Date de publication:
03 09 2019
Historique:
received: 10 04 2019
revised: 21 05 2019
accepted: 17 06 2019
pubmed: 16 7 2019
medline: 13 5 2020
entrez: 16 7 2019
Statut: ppublish

Résumé

The unique membrane composition of cilia is maintained by a diffusion barrier at the transition zone that is breached when the BBSome escorts signaling receptors out of cilia. Understanding how the BBSome removes proteins from cilia has been hampered by a lack of structural information. Here, we present a nearly complete Cα model of BBSome purified from cow retina. The model is based on a single-particle cryo-electron microscopy density map at 4.9-Å resolution that was interpreted with the help of comprehensive Rosetta-based structural modeling constrained by crosslinking mass spectrometry data. We find that BBSome subunits have a very high degree of interconnectivity, explaining the obligate nature of the complex. Furthermore, like other coat adaptors, the BBSome exists in an autoinhibited state in solution and must thus undergo a conformational change upon recruitment to membranes by the small GTPase ARL6/BBS3. Our model provides the first detailed view of the machinery enabling ciliary exit.

Identifiants

pubmed: 31303482
pii: S0969-2126(19)30205-9
doi: 10.1016/j.str.2019.06.006
pmc: PMC6726506
mid: NIHMS1532937
pii:
doi:

Substances chimiques

Microtubule-Associated Proteins 0
ADP-Ribosylation Factors EC 3.6.5.2

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1384-1394.e4

Subventions

Organisme : NIGMS NIH HHS
ID : P41 GM103311
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIGMS NIH HHS
ID : F32 GM089218
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM123089
Pays : United States
Organisme : Austrian Science Fund FWF
ID : P 30162
Pays : Austria
Organisme : NIGMS NIH HHS
ID : R01 GM089933
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY002162
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

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Auteurs

Hui-Ting Chou (HT)

Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

Luise Apelt (L)

Department of Molecular and Cellular Physiology, Stanford University School of Medicine, CA 94305, USA.

Daniel P Farrell (DP)

Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.

Susan Roehl White (SR)

Department of Molecular and Cellular Physiology, Stanford University School of Medicine, CA 94305, USA.

Jonathan Woodsmith (J)

Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz and BioTechMed-Graz, Graz, Austria.

Vladimir Svetlov (V)

Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA.

Jaclyn S Goldstein (JS)

Department of Molecular and Cellular Physiology, Stanford University School of Medicine, CA 94305, USA.

Andrew R Nager (AR)

Department of Molecular and Cellular Physiology, Stanford University School of Medicine, CA 94305, USA.

Zixuan Li (Z)

Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA.

Jean Muller (J)

Laboratoire de Génétique Médicale, UMR_S INSERM U1112, IGMA, Faculté de Médecine FMTS, Université de Strasbourg, 67091 Strasbourg, France; Laboratoires de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, 67091 Strasbourg, France.

Hélène Dollfus (H)

Laboratoire de Génétique Médicale, UMR_S INSERM U1112, IGMA, Faculté de Médecine FMTS, Université de Strasbourg, 67091 Strasbourg, France; Centre de Référence pour les Affections Rares en Génétique Ophtalmologique, CARGO, Filière SENSGENE, Hôpitaux Universitaires de Strasbourg, 67091 Strasbourg, France.

Evgeny Nudler (E)

Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA.

Ulrich Stelzl (U)

Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz and BioTechMed-Graz, Graz, Austria.

Frank DiMaio (F)

Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA. Electronic address: dimaio@u.washington.edu.

Maxence V Nachury (MV)

Department of Molecular and Cellular Physiology, Stanford University School of Medicine, CA 94305, USA; Department of Ophthalmology, University of California San Francisco, San Francisco, CA 94143, USA. Electronic address: maxence.nachury@ucsf.edu.

Thomas Walz (T)

Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Laboratory of Molecular Electron Microscopy, The Rockefeller University, New York, NY 10065, USA. Electronic address: twalz@rockefeller.edu.

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Classifications MeSH