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-Structure paper
タイトル | Structures of the fungal dynamin-related protein Vps1 reveal a unique, open helical architecture. |
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ジャーナル・号・ページ | J Cell Biol, Vol. 217, Issue 10, Page 3608-3624, Year 2018 |
掲載日 | 2018年10月1日 |
著者 | Natalia V Varlakhanova / Frances J D Alvarez / Tyler M Brady / Bryan A Tornabene / Christopher J Hosford / Joshua S Chappie / Peijun Zhang / Marijn G J Ford / |
PubMed 要旨 | Dynamin-related proteins (DRPs) are large multidomain GTPases required for diverse membrane-remodeling events. DRPs self-assemble into helical structures, but how these structures are tailored to ...Dynamin-related proteins (DRPs) are large multidomain GTPases required for diverse membrane-remodeling events. DRPs self-assemble into helical structures, but how these structures are tailored to their cellular targets remains unclear. We demonstrate that the fungal DRP Vps1 primarily localizes to and functions at the endosomal compartment. We present crystal structures of a Vps1 GTPase-bundle signaling element (BSE) fusion in different nucleotide states to capture GTP hydrolysis intermediates and concomitant conformational changes. Using cryoEM, we determined the structure of full-length GMPPCP-bound Vps1. The Vps1 helix is more open and flexible than that of dynamin. This is due to further opening of the BSEs away from the GTPase domains. A novel interface between adjacent GTPase domains forms in Vps1 instead of the contacts between the BSE and adjacent stalks and GTPase domains as seen in dynamin. Disruption of this interface abolishes Vps1 function in vivo. Hence, Vps1 exhibits a unique helical architecture, highlighting structural flexibilities of DRP self-assembly. |
リンク | J Cell Biol / PubMed:30087125 / PubMed Central |
手法 | EM (らせん対称) / X線回折 |
解像度 | 2.26 - 11.0 Å |
構造データ | EMDB-7874: PDB-6def: PDB-6di7: PDB-6djq: |
化合物 | ChemComp-GCP: ChemComp-MG: ChemComp-HOH: ChemComp-GDP: ChemComp-ALF: ChemComp-NA: |
由来 |
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キーワード | HYDROLASE / Vps1 / Vacuolar Protein Sorting 1 / Dynamin-Related Protein / DRP / GTPase / GMPPCP / Endosome / Vacuole / GDP / dynamin / GDP.AlF4- / transition state |