1. Structural Biology and Molecular Biophysics

Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex

  1. Guijun Shang
  2. Chad A Brautigam
  3. Rui Chen
  4. Defen Lu
  5. Jesús Torres-Vázquez
  6. Xuewu Zhang  Is a corresponding author
  1. University of Texas Southwestern Medical Center, United States
  2. New York University Langone Medical Center, United States
https://doi.org/10.7554/eLife.27322
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Cite this article
  1. Guijun Shang
  2. Chad A Brautigam
  3. Rui Chen
  4. Defen Lu
  5. Jesús Torres-Vázquez
  6. Xuewu Zhang
(2017)
Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex
eLife 6:e27322.
https://doi.org/10.7554/eLife.27322
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Abstract

The GIPC family adaptor proteins mediate endocytosis by tethering cargo proteins to the myosin VI motor. The structural mechanisms for the GIPC/cargo and GIPC/myosin VI interactions remained unclear. PlexinD1, a transmembrane receptor that regulates neuronal and cardiovascular development, is a cargo of GIPCs. GIPC-mediated endocytic trafficking regulates PlexinD1 signaling. Here we unravel the mechanisms of the interactions among PlexinD1, GIPCs and myosin VI by a series of crystal structures of these proteins in apo or bound states. GIPC1 forms a domain-swapped dimer in an autoinhibited conformation that hinders binding of both PlexinD1 and myosin VI. PlexinD1 binding to GIPC1 releases the autoinhibition, promoting its interaction with myosin VI. GIPCs and myosin VI interact through two distinct interfaces and form an open-ended alternating array. Our data support that this alternating array underlies the oligomerization of the GIPC/Myosin VI complexes in solution and cells.

Data availability

The following data sets were generated
    1. Shang G
    2. Zhang X
    (2017) Structure of apo-PlexinD1
    Publicly available at the RCSB Protein Data Bank (accession no: 5V6R).
    http://www.rcsb.org/pdb/explore/explore.do?structureId=5V6R
    1. Shang G
    2. Zhang X
    (2017) Structure of apo-GIPC1
    Publicly available at the RCSB Protein Data Bank (accession no: 5V6B).
    http://www.rcsb.org/pdb/explore/explore.do?structureId=5V6B
    1. Shang G
    2. Zhang X
    (2017) Structure of the PlexinD1/GIPC1 complex
    Publicly available at the RCSB Protein Data Bank (accession no: 5V6T).
    http://www.rcsb.org/pdb/explore/explore.do?structureId=5V6T
    1. Shang G
    2. Zhang X
    (2017) Structure of the GIPC1-GH2/Myosin VI-HCBD complex
    Publicly available at the RCSB Protein Data Bank (accession no: 5V6E).
    http://www.rcsb.org/pdb/explore/explore.do?structureId=5V6E
    1. Shang G
    2. Zhang X
    (2017) Structure of the GIPC2-GH2/Myosin VI-HCBD complex
    Publicly available at the RCSB Protein Data Bank (accession no: 5V6H).
    http://www.rcsb.org/pdb/explore/explore.do?structureId=5V6H

Article and author information

Author details

  1. Guijun Shang

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

  2. Chad A Brautigam

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

  3. Rui Chen

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

  4. Defen Lu

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

  5. Jesús Torres-Vázquez

    Department of Cell Biology, New York University Langone Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Xuewu Zhang

    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    xuewu.zhang@utsouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3634-6711

Funding

National Institutes of Health (GM088197)

  • Guijun Shang
  • Rui Chen
  • Xuewu Zhang

Welch Foundation (I-1702)

  • Guijun Shang
  • Rui Chen
  • Xuewu Zhang

National Institutes of Health (R01HL133687)

  • Jesús Torres-Vázquez

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

Copyright

© 2017, Shang 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. Guijun Shang
  2. Chad A Brautigam
  3. Rui Chen
  4. Defen Lu
  5. Jesús Torres-Vázquez
  6. Xuewu Zhang
(2017)
Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex
eLife 6:e27322.
https://doi.org/10.7554/eLife.27322

Share this article

https://doi.org/10.7554/eLife.27322

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