1. Biochemistry and Chemical Biology
  2. Cell Biology
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Implications of the differing roles of the β1 and β3 transmembrane and cytoplasmic domains for integrin function

  1. Zhenwei Lu
  2. Sijo Mathew
  3. Jiang Chen
  4. Arina Hadziselimovic
  5. Riya Palamuttam
  6. Billy G Hudson
  7. Reinhard Fässler
  8. Ambra Pozzi
  9. Charles R Sanders  Is a corresponding author
  10. Roy Zent  Is a corresponding author
  1. Vanderbilt University Medical Center, United States
  2. Vanderbilt Medical Center, United States
  3. Virginia Tech, United States
  4. Max Planck Institute of Biochemistry, Germany
Research Article
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Cite this article as: eLife 2016;5:e18633 doi: 10.7554/eLife.18633

Abstract

Integrins are transmembrane receptors composed of α and β subunits. Although most integrins contain β1, canonical activation mechanisms are based on studies of the platelet integrin, αIIbβ3. Its inactive conformation is characterized by association of the αIIb transmembrane and cytosolic domain (TM/CT) with a tilted β3 TM/CT that leads to activation when disrupted. We show significant structural differences between β1 and β3 TM/CT in bicelles. Moreover, the 'snorkeling' lysine at the TM/CT interface of β subunits, previously proposed to regulate αIIbβ3 activation by ion pairing with nearby lipids, plays opposite roles in β1 and β3 integrin function and in neither case is responsible for TM tilt. Affinities ranging from almost no interaction to the relatively high avidity that characterizes αIIbβ3 exist between various α subunits and β1 TM/CTs. The αIIbβ3-based canonical model for the roles of the TM/CT in integrin activation and function clearly does not extend to all mammalian integrins.

Article and author information

Author details

  1. Zhenwei Lu

    Department of Biochemistry, Vanderbilt University Medical Center, Nashville, United States
    Competing interests
    No competing interests declared.
  2. Sijo Mathew

    Division of Nephrology, Department of Medicine, Vanderbilt Medical Center, Nashville, United States
    Competing interests
    No competing interests declared.
  3. Jiang Chen

    Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, United States
    Competing interests
    No competing interests declared.
  4. Arina Hadziselimovic

    Department of Biochemistry, Vanderbilt University Medical Center, Nashville, United States
    Competing interests
    No competing interests declared.
  5. Riya Palamuttam

    Department of Biochemistry, Vanderbilt University Medical Center, Nashville, United States
    Competing interests
    No competing interests declared.
  6. Billy G Hudson

    Department of Biochemistry, Vanderbilt University Medical Center, Nashville, United States
    Competing interests
    No competing interests declared.
  7. Reinhard Fässler

    Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany
    Competing interests
    Reinhard Fässler, Reviewing editor, eLife.
  8. Ambra Pozzi

    Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States
    Competing interests
    Ambra Pozzi, Reviewing editor, eLife.
  9. Charles R Sanders

    Department of Biochemistry, Vanderbilt University Medical Center, Nashville, United States
    For correspondence
    chuck.sanders@vanderbilt.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2046-2862
  10. Roy Zent

    Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States
    For correspondence
    roy.zent@vanderbilt.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2983-8133

Funding

Veterans Affairs San Diego Healthcare System

  • Ambra Pozzi
  • Roy Zent

National Institutes of Health

  • Billy G Hudson
  • Ambra Pozzi
  • Charles R Sanders
  • Roy Zent

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

Reviewing Editor

  1. Maddy Parsons, King's College London, United Kingdom

Publication history

  1. Received: June 9, 2016
  2. Accepted: December 7, 2016
  3. Accepted Manuscript published: December 8, 2016 (version 1)
  4. Accepted Manuscript updated: December 9, 2016 (version 2)
  5. Accepted Manuscript updated: December 9, 2016 (version 3)
  6. Version of Record published: January 3, 2017 (version 4)
  7. Version of Record updated: January 4, 2017 (version 5)

Copyright

© 2016, Lu 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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