1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics

Structural Basis of Protein Translocation by the Vps4-Vta1 AAA ATPase

  1. Nicole Monroe
  2. Han Han
  3. Peter S Shen  Is a corresponding author
  4. Wesley I Sundquist  Is a corresponding author
  5. Christopher P Hill  Is a corresponding author
  1. University of Utah School of Medicine, United States
https://doi.org/10.7554/eLife.24487
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  1. Nicole Monroe
  2. Han Han
  3. Peter S Shen
  4. Wesley I Sundquist
  5. Christopher P Hill
(2017)
Structural Basis of Protein Translocation by the Vps4-Vta1 AAA ATPase
eLife 6:e24487.
https://doi.org/10.7554/eLife.24487
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Abstract

Many important cellular membrane fission reactions are driven by ESCRT pathways, which culminate in disassembly of ESCRT-III polymers by the AAA ATPase Vps4. We report a 4.3 Å resolution cryo-EM structure of the active Vps4 hexamer with its cofactor Vta1, ADP•BeFx, and an ESCRT-III substrate peptide. Four Vps4 subunits form a helix whose interfaces are consistent with ATP-binding, is stabilized by Vta1, and binds the substrate peptide. The fifth subunit approximately continues this helix but appears to be dissociating. The final Vps4 subunit completes a notched-washer configuration as if transitioning between the ends of the helix. We propose that ATP binding propagates growth at one end of the helix while hydrolysis promotes disassembly at the other end, so that Vps4 'walks' along ESCRT-III until it encounters the ordered N-terminal domain to destabilize the ESCRT-III lattice. This model may be generally applicable to other protein-translocating AAA ATPases.

Data availability

The following data sets were generated
    1. Monroe N
    2. Han H
    3. Shen PS
    4. Sundquist WI
    5. Hill CP
    (2017) Vps4-Vta1 complex
    Publicly available at the RCSB Protein Data Bank (accession no: 5UIE).
    http://www.rcsb.org/pdb/explore/explore.do?structureId=5UIE
    1. Monroe N
    2. Han H
    3. Shen PS
    4. Sundquist WI
    5. Hill CP
    (2017) Vps4-Vta1 complex
    Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-8549).
    http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-8549
    1. Monroe N
    2. Han H
    3. Shen PS
    4. Sundquist WI
    5. Hill CP
    (2017) Vps4-Vta1 complex_sharpened map
    Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-8550).
    http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-8550
    1. Monroe N
    2. Han H
    3. Shen PS
    4. Sundquist WI
    5. Hill CP
    (2017) Vps4-HCP hexamer
    Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-8551).
    http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-8551
    1. Monroe N
    2. Han H
    3. Shen PS
    4. Sundquist WI
    5. Hill CP
    (2017) Vps4-Vta1 complex_VSL_A
    Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-8552).
    http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-8552
    1. Monroe N
    2. Han H
    3. Shen PS
    4. Sundquist WI
    5. Hill CP
    (2017) Vps4-Vta1 complex_VSL_B
    Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-8553).
    http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-8553
    1. Monroe N
    2. Han H
    3. Shen PS
    4. Sundquist WI
    5. Hill CP
    (2017) Vps4-Vta1 complex_VSL_C
    Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-8554).
    http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-8554
    1. Monroe N
    2. Han H
    3. Shen PS
    4. Sundquist WI
    5. Hill CP
    (2017) Vps4-Vta1 complex_VSL_D
    Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-8555).
    http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-8555
    1. Monroe N
    2. Han H
    3. Shen PS
    4. Sundquist WI
    5. Hill CP
    (2017) Vps4-Vta1 complex_VSL_E
    Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-8556).
    http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-8556
    1. Monroe N
    2. Han H
    3. Shen PS
    4. Sundquist WI
    5. Hill CP
    (2017) Vps4-Vta1 complex_VSL_F
    Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-8557).
    http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-8557
    1. Monroe N
    2. Han H
    3. Shen PS
    4. Sundquist WI
    5. Hill CP
    (2017) Vps4-Vta1 complex, State 3 of subunitF
    Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-8570).
    http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-8570
    1. Monroe N
    2. Han H
    3. Shen PS
    4. Sundquist WI
    5. Hill CP
    (2017) Vps4-Vta1 complex, State 2 of subunitF
    Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-8571).
    http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-8571
    1. Monroe N
    2. Han H
    3. Shen PS
    4. Sundquist WI
    5. Hill CP
    (2017) Vps4-Vta1 complex, State 1 of subunitF
    Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-8572).
    http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-8572

Article and author information

Author details

  1. Nicole Monroe

    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7678-4997

  2. Han Han

    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    No competing interests declared.

  3. Peter S Shen

    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    For correspondence
    peter.shen@biochem.utah.edu
    Competing interests
    No competing interests declared.

  4. Wesley I Sundquist

    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    For correspondence
    wes@biochem.utah.edu
    Competing interests
    Wesley I Sundquist, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9988-6021

  5. Christopher P Hill

    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    For correspondence
    chris@biochem.utah.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6796-7740

Funding

National Institutes of Health (P50 GM082545)

  • Nicole Monroe
  • Han Han
  • Peter S Shen
  • Wesley I Sundquist
  • Christopher P Hill

National Institutes of Health (Microbial Pathogenesis Training Grant T32 AI055434)

  • Nicole Monroe

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Sriram Subramaniam, National Cancer Institute, United States

Version history

  1. Received: December 21, 2016
  2. Accepted: April 4, 2017
  3. Accepted Manuscript published: April 5, 2017 (version 1)
  4. Version of Record published: May 2, 2017 (version 2)

Copyright

© 2017, Monroe et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Nicole Monroe
  2. Han Han
  3. Peter S Shen
  4. Wesley I Sundquist
  5. Christopher P Hill
(2017)
Structural Basis of Protein Translocation by the Vps4-Vta1 AAA ATPase
eLife 6:e24487.
https://doi.org/10.7554/eLife.24487

Share this article

https://doi.org/10.7554/eLife.24487

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