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-Structure paper
タイトル | Structure and activation mechanism of the BBSome membrane protein trafficking complex. |
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ジャーナル・号・ページ | Elife, Vol. 9, Year 2020 |
掲載日 | 2020年1月15日 |
![]() | Sandeep K Singh / Miao Gui / Fujiet Koh / Matthew Cj Yip / Alan Brown / ![]() |
PubMed 要旨 | 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 ...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. |
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手法 | EM (単粒子) |
解像度 | 3.1 - 3.5 Å |
構造データ | EMDB-21144, PDB-6vbu: EMDB-21145, PDB-6vbv: |
化合物 | ![]() ChemComp-CA: ![]() ChemComp-GTP: |
由来 |
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![]() | PROTEIN TRANSPORT / Cilia / ciliopathy / complex / membrane-protein transport |