Insights into the key determinants of membrane protein topology enable the identification of new monotopic folds

  1. Sonya Entova
  2. Jean-Marc Billod
  3. Jean-Marie Swiecicki
  4. Sonsoles Martin-Santamaria
  5. Barbara Imperiali  Is a corresponding author
  1. Massachusetts Institute of Technology, United States
  2. Centro de Investigaciones Biológicas - CIB-CSIC, Spain

Abstract

Monotopic membrane proteins integrate into the lipid bilayer via reentrant hydrophobic domains that enter and exit on a single face of the membrane. Whereas many membrane-spanning proteins have been structurally characterized and transmembrane topologies can be predicted computationally, relatively little is known about the determinants of membrane topology in monotopic proteins. Recently, we reported the X-ray structure determination of PglC, a full-length monotopic membrane protein with phosphoglycosyl transferase (PGT) activity. The definition of this unique structure has prompted in vivo, biochemical, and computational analyses to understand and define two key motifs that contribute to the membrane topology and to provide insight into the dynamics of the enzyme in a lipid bilayer environment. Using the new information gained from studies on the PGT superfamily we demonstrate that the two motifs exemplify principles of topology determination that can be applied to the identification of reentrant domains among diverse monotopic proteins of interest.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Sonya Entova

    Department of Biology, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5270-3336
  2. Jean-Marc Billod

    Department of Structural and Chemical Biology, Centro de Investigaciones Biológicas - CIB-CSIC, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. Jean-Marie Swiecicki

    Department of Biology, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7139-8621
  4. Sonsoles Martin-Santamaria

    Department of Structural and Chemical Biology, Centro de Investigaciones Biológicas - CIB-CSIC, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. Barbara Imperiali

    Department of Biology, Massachusetts Institute of Technology, Cambridge, United States
    For correspondence
    imper@mit.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5749-7869

Funding

NIH Office of the Director (NIH GM-039334)

  • Sonya Entova
  • Barbara Imperiali

Ministerio de Economía y Competitividad (CTQ2014-57141-R)

  • Jean-Marc Billod
  • Sonsoles Martin-Santamaria

Jane Coffin Childs Memorial Fund for Medical Research

  • Jean-Marie Swiecicki

NIH Office of the Director (T32-GM007287)

  • Sonya Entova

Ministerio de Economía y Competitividad (CTQ2017-88353-R)

  • Jean-Marc Billod
  • Sonsoles Martin-Santamaria

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

Reviewing Editor

  1. Volker Dötsch, J.W. Goethe-University, Germany

Publication history

  1. Received: August 8, 2018
  2. Accepted: August 27, 2018
  3. Accepted Manuscript published: August 31, 2018 (version 1)
  4. Version of Record published: September 11, 2018 (version 2)

Copyright

© 2018, Entova 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. Sonya Entova
  2. Jean-Marc Billod
  3. Jean-Marie Swiecicki
  4. Sonsoles Martin-Santamaria
  5. Barbara Imperiali
(2018)
Insights into the key determinants of membrane protein topology enable the identification of new monotopic folds
eLife 7:e40889.
https://doi.org/10.7554/eLife.40889
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