Structural basis of Vta1 function in the multivesicular body sorting pathway |
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Authors: | Xiao Junyu Xia Hengchuan Zhou Jiahai Azmi Ishara F Davies Brian A Katzmann David J Xu Zhaohui |
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Affiliation: | Life Sciences Institute and Department of Biological Chemistry, Medical School, University of Michigan, Ann Arbor, MI 48109, USA. |
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Abstract: | The MVB pathway plays essential roles in several eukaryotic cellular processes. Proper function of the MVB pathway requires reversible membrane association of the ESCRTs, a process catalyzed by Vps4 ATPase. Vta1 regulates the Vps4 activity, but its mechanism of action was poorly understood. We report the high-resolution crystal structures of the Did2- and Vps60-binding N-terminal domain and the Vps4-binding C-terminal domain of S. cerevisiae Vta1. The C-terminal domain also mediates Vta1 dimerization and both subunits are required for its function as a Vps4 regulator. Emerging from our analysis is a mechanism of regulation by Vta1 in which the C-terminal domain stabilizes the ATP-dependent double ring assembly of Vps4. In addition, the MIT motif-containing N-terminal domain, projected by a long disordered linker, allows contact between the Vps4 disassembly machinery and the accessory ESCRT-III proteins. This provides an additional level of regulation and coordination for ESCRT-III assembly and disassembly. |
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