1. Structural Biology and Molecular Biophysics

Cryo-EM structure of VASH1-SVBP bound to microtubules

  1. Faxiang Li
  2. Yang Li
  3. Xuecheng Ye
  4. Haishan Gao
  5. Zhubing Shi
  6. Xuelian Luo
  7. Luke M Rice  Is a corresponding author
  8. Hongtao Yu  Is a corresponding author
  1. University of Texas Southwestern Medical Center, United States
  2. Westlake University, China
https://doi.org/10.7554/eLife.58157
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Cite this article
  1. Faxiang Li
  2. Yang Li
  3. Xuecheng Ye
  4. Haishan Gao
  5. Zhubing Shi
  6. Xuelian Luo
  7. Luke M Rice
  8. Hongtao Yu
(2020)
Cryo-EM structure of VASH1-SVBP bound to microtubules
eLife 9:e58157.
https://doi.org/10.7554/eLife.58157
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Abstract

The dynamic tyrosination-detyrosination cycle of α-tubulin regulates microtubule functions. Perturbation of this cycle impairs mitosis, neural physiology, and cardiomyocyte contraction. The carboxypeptidases vasohibins 1 and 2 (VASH1 and VASH2), in complex with the small vasohibin-binding protein (SVBP), mediate α-tubulin detyrosination. These enzymes detyrosinate microtubules more efficiently than soluble αβ-tubulin heterodimers. The structural basis for this substrate preference is not understood. Using cryo-electron microscopy (cryo-EM), we have determined the structure of human VASH1-SVBP bound to microtubules. The acidic C-terminal tail of α-tubulin binds to a positively charged groove near the active site of VASH1. VASH1 forms multiple additional contacts with the globular domain of α-tubulin, including contacts with a second α-tubulin in an adjacent protofilament. Simultaneous engagement of two protofilaments by VASH1 can only occur within the microtubule lattice, but not with free αβ heterodimers. These lattice-specific interactions enable preferential detyrosination of microtubules by VASH1.

Data availability

Coordinates and EM density maps have been deposited into the Protein Data Bank under the accession code 6WSL and EMD-21893, respectively.

The following data sets were generated

Article and author information

Author details

  1. Faxiang Li

    Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Yang Li

    Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Xuecheng Ye

    Departments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Haishan Gao

    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4954-8793

  5. Zhubing Shi

    Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9624-4960

  6. Xuelian Luo

    Departments of Pharmacology and Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5058-4695

  7. Luke M Rice

    Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    Luke.Rice@UTSouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6551-3307

  8. Hongtao Yu

    Laboratory of Cell Biology, Westlake University, Hangzhou, Zhejiang Province, China
    For correspondence
    yuhongtao@westlake.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8861-049X

Funding

National Institutes of Health (GM107415)

  • Xuelian Luo

National Institutes of Health (GM098543)

  • Luke M Rice

Cancer Prevention and Research Institute of Texas (RP160255)

  • Xuelian Luo

Cancer Prevention and Research Institute of Texas (RP160667-P2)

  • Hongtao Yu

Welch Foundation (I-1932)

  • Xuelian Luo

Welch Foundation (I-1908)

  • Luke M Rice

Welch Foundation (I-1441)

  • Hongtao Yu

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

Reviewing Editor

  1. Thomas Surrey, Centre for Genomic Regulation (CRG), Spain

Version history

  1. Received: April 22, 2020
  2. Accepted: August 7, 2020
  3. Accepted Manuscript published: August 10, 2020 (version 1)
  4. Version of Record published: August 26, 2020 (version 2)

Copyright

© 2020, Li 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. Faxiang Li
  2. Yang Li
  3. Xuecheng Ye
  4. Haishan Gao
  5. Zhubing Shi
  6. Xuelian Luo
  7. Luke M Rice
  8. Hongtao Yu
(2020)
Cryo-EM structure of VASH1-SVBP bound to microtubules
eLife 9:e58157.
https://doi.org/10.7554/eLife.58157

Share this article

https://doi.org/10.7554/eLife.58157

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