Structural Basis of Vta1 Function in the Multivesicular Body Sorting Pathway

Junyu Xiao; Hengchuan Xia; Jiahai Zhou; Ishara F. Azmi; Brian A. Davies; David J. Katzmann; Zhaohui Xu

doi:10.1016/j.devcel.2007.10.013

Structural Basis of Vta1 Function in the Multivesicular Body Sorting Pathway

Junyu Xiao, Hengchuan Xia, Jiahai Zhou, Ishara F. Azmi, Brian A. Davies, David J. Katzmann, Zhaohui Xu

Biochemistry and Molecular Biology

Research output: Contribution to journal › Article › peer-review

85 Scopus citations

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.

Original language	English (US)
Pages (from-to)	37-49
Number of pages	13
Journal	Developmental Cell
Volume	14
Issue number	1
DOIs	https://doi.org/10.1016/j.devcel.2007.10.013
State	Published - Jan 15 2008

Keywords

CELLBIO

ASJC Scopus subject areas

Molecular Biology
Biochemistry, Genetics and Molecular Biology(all)
Developmental Biology
Cell Biology

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title = "Structural Basis of Vta1 Function in the Multivesicular Body Sorting Pathway",

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.",

keywords = "CELLBIO",

author = "Junyu Xiao and Hengchuan Xia and Jiahai Zhou and Azmi, {Ishara F.} and Davies, {Brian A.} and Katzmann, {David J.} and Zhaohui Xu",

note = "Funding Information: We thank staffs of the Center for Structural Biology at the University of Michigan for maintaining the X-ray facility and at the Advanced Photon Source beam lines 21-ID and 23-ID of Argonne National Laboratory for access and help with data collection; K. Yoshino-Koh for help at the early stage of this project; X. Chen for technical assistance; M. Amenta-Ilbert and U. Jakob for access and help with CD spectral analysis; and R. Matthews, J. Tesmer and L. Weisman for critically reading the manuscript. This work was supported in part by NIH grants to Z.X. (R01-DK65980) and D.J.K. (R01-GM 73024). I.F.A. is supported by a predoctoral fellowship from the American Heart Association (AHA 07-155882). ",

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doi = "10.1016/j.devcel.2007.10.013",

language = "English (US)",

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AU - Xiao, Junyu

AU - Xia, Hengchuan

AU - Zhou, Jiahai

AU - Azmi, Ishara F.

AU - Davies, Brian A.

AU - Katzmann, David J.

AU - Xu, Zhaohui

N1 - Funding Information: We thank staffs of the Center for Structural Biology at the University of Michigan for maintaining the X-ray facility and at the Advanced Photon Source beam lines 21-ID and 23-ID of Argonne National Laboratory for access and help with data collection; K. Yoshino-Koh for help at the early stage of this project; X. Chen for technical assistance; M. Amenta-Ilbert and U. Jakob for access and help with CD spectral analysis; and R. Matthews, J. Tesmer and L. Weisman for critically reading the manuscript. This work was supported in part by NIH grants to Z.X. (R01-DK65980) and D.J.K. (R01-GM 73024). I.F.A. is supported by a predoctoral fellowship from the American Heart Association (AHA 07-155882).

PY - 2008/1/15

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N2 - 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.

AB - 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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Structural Basis of Vta1 Function in the Multivesicular Body Sorting Pathway

Abstract

Keywords

ASJC Scopus subject areas

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