1. Structural Biology and Molecular Biophysics
  2. Microbiology and Infectious Disease

Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1

  1. Xiaofei Jia
  2. Erin Weber
  3. Andrey Tokarev
  4. Mary Lewinski
  5. Maryan Rizk
  6. Marissa Suarez
  7. John Guatelli
  8. Yong Xiong  Is a corresponding author
  1. Yale University, United States
  2. University of California San Diego, United States
https://doi.org/10.7554/eLife.02362
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Cite this article
  1. Xiaofei Jia
  2. Erin Weber
  3. Andrey Tokarev
  4. Mary Lewinski
  5. Maryan Rizk
  6. Marissa Suarez
  7. John Guatelli
  8. Yong Xiong
(2014)
Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1
eLife 3:e02362.
https://doi.org/10.7554/eLife.02362
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Abstract

BST2/tetherin, an antiviral restriction factor, inhibits the release of enveloped viruses from the cell surface. Human immunodeficiency virus-1 (HIV-1) antagonizes BST2 through viral protein u (Vpu), which downregulates BST2 from the cell surface. We report the crystal structure of a protein complex containing Vpu and BST2 cytoplasmic domains and the core of the clathrin adaptor protein complex 1 (AP1). This, together with our biochemical and functional validations, reveals how Vpu hijacks the AP1-dependent membrane trafficking pathways to mistraffick BST2. Vpu mimics a canonical acidic dileucine-sorting motif to bind AP1 in the cytosol, while simultaneously interacting with BST2 in the membrane. These interactions enable Vpu to build on an intrinsic interaction between BST2 and AP1, presumably causing the observed retention of BST2 in juxtanuclear endosomes and stimulating its degradation in lysosomes. The ability of Vpu to hijack AP-dependent trafficking pathways suggests a potential common theme for Vpu-mediated downregulation of host proteins.

Article and author information

Author details

  1. Xiaofei Jia

    Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Erin Weber

    Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Andrey Tokarev

    University of California San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Mary Lewinski

    University of California San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Maryan Rizk

    University of California San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Marissa Suarez

    University of California San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. John Guatelli

    University of California San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Yong Xiong

    Yale University, New Haven, United States
    For correspondence
    yong.xiong@yale.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Wesley Sundquist, University of Utah, United States

Version history

  1. Received: January 21, 2014
  2. Accepted: April 6, 2014
  3. Accepted Manuscript published: April 29, 2014 (version 1)
  4. Version of Record published: May 13, 2014 (version 2)

Copyright

© 2014, Jia et al.

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

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  1. Xiaofei Jia
  2. Erin Weber
  3. Andrey Tokarev
  4. Mary Lewinski
  5. Maryan Rizk
  6. Marissa Suarez
  7. John Guatelli
  8. Yong Xiong
(2014)
Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1
eLife 3:e02362.
https://doi.org/10.7554/eLife.02362

Share this article

https://doi.org/10.7554/eLife.02362

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