6VBU

Structure of the bovine BBSome complex

Summary for 6VBU

• Entry DOI: 10.2210/pdb6vbu/pdb
• EMDB information: 21144
• Descriptor: Bardet-Biedl syndrome 18 protein, BBS1 domain-containing protein, Bardet-Biedl syndrome 2 protein homolog, ... (9 entities in total)
• Functional Keywords: cilia, ciliopathy, complex, membrane-protein transport, protein transport
• Biological source: Bos taurus (Bovine); More
• Total number of polymer chains: 8
• Total formula weight: 486560.10

Authors

Singh, S.K.,Gui, M.,Koh, F.,Yip, M.C.J.,Brown, A. (deposition date: 2019-12-19, release date: 2020-01-29, Last modification date: 2024-03-06)

Primary citation

Singh, S.K.,Gui, M.,Koh, F.,Yip, M.C.,Brown, A.
Structure and activation mechanism of the BBSome membrane protein trafficking complex.
Elife, 9:-, 2020

PubMed Abstract: Bardet-Biedl syndrome (BBS) is a currently incurable ciliopathy caused by the failure to correctly establish or maintain cilia-dependent signaling pathways. Eight proteins associated with BBS assemble into the BBSome, a key regulator of the ciliary membrane proteome. We report the electron cryomicroscopy (cryo-EM) structures of the native bovine BBSome in inactive and active states at 3.1 and 3.5 Å resolution, respectively. In the active state, the BBSome is bound to an Arf-family GTPase (ARL6/BBS3) that recruits the BBSome to ciliary membranes. ARL6 recognizes a composite binding site formed by BBS1 and BBS7 that is occluded in the inactive state. Activation requires an unexpected swiveling of the β-propeller domain of BBS1, the subunit most frequently implicated in substrate recognition, which widens a central cavity of the BBSome. Structural mapping of disease-causing mutations suggests that pathogenesis results from folding defects and the disruption of autoinhibition and activation.

PubMed: 31939736
DOI: 10.7554/eLife.53322

Experimental method

ELECTRON MICROSCOPY (3.1 Å)