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Structural basis of Vta1 function in the multi‐vesicular body sorting pathway
Author(s) -
Xiao Junyu,
Xia Hengchuan,
Zhou Jiahai,
Azmi Ishara,
Davies Brian A,
Katzmann David J,
Xu Zhaohui
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.816.2
Subject(s) - microbiology and biotechnology , aaa proteins , escrt , vesicular transport proteins , linker , c terminus , chemistry , saccharomyces cerevisiae , protein targeting , regulator , vacuolar protein sorting , atpase , endosome , biophysics , biology , biochemistry , membrane protein , membrane , gene , intracellular , amino acid , enzyme , computer science , operating system
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.