1. Structural Biology and Molecular Biophysics
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Structure of MlaFB uncovers novel mechanisms of ABC transporter regulation

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Cite this article as: eLife 2020;9:e60030 doi: 10.7554/eLife.60030

Abstract

ABC transporters facilitate the movement of diverse molecules across cellular membranes, but how their activity is regulated post-translationally is not well understood. Here we report the crystal structure of MlaFB from E. coli, the cytoplasmic portion of the larger MlaFEDB ABC transporter complex, which drives phospholipid trafficking across the bacterial envelope to maintain outer membrane integrity. MlaB, a STAS domain protein, binds the ABC nucleotide binding domain, MlaF, and is required for its stability. Our structure also implicates a unique C-terminal tail of MlaF in self-dimerization. Both the C-terminal tail of MlaF and the interaction with MlaB are required for the proper assembly of the MlaFEDB complex and its function in cells. This work leads to a new model for how an important bacterial lipid transporter may be regulated by small proteins, and raises the possibility that similar regulatory mechanisms may exist more broadly across the ABC transporter family.

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Author details

  1. Ljuvica R Kolich

    Department of Cell Biology, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6696-9645
  2. Ya-Ting Chang

    Department of Cell Biology, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Nicolas Coudray

    Department of Cell Biology and Applied Bioinformatics Laboratory, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Sabrina I Giacometti

    Department of Cell Biology, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Mark R MacRae

    Department of Cell Biology, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4941-9526
  6. Georgia L Isom

    Department of Cell Biology, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Evelyn M Teran

    Department of Cell Biology, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Gira Bhabha

    Department of Cell Biology, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0624-6178
  9. Damian C Ekiert

    Department of Cell Biology and Department of Microbiology, New York University School of Medicine, New York, United States
    For correspondence
    damian.ekiert@EKIERTLAB.ORG
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2570-0404

Funding

American Heart Association (20POST35210202)

  • Georgia L Isom

National Institutes of Health (T32 GM088118)

  • Mark R MacRae

National Institutes of Health (R35GM128777)

  • Damian C Ekiert

Damon Runyon Cancer Research Foundation (DFS‐20‐16)

  • Gira Bhabha

National Institutes of Health (R00GM112982)

  • Gira Bhabha

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

Reviewing Editor

  1. László Csanády, Semmelweis University, Hungary

Publication history

  1. Received: June 15, 2020
  2. Accepted: June 24, 2020
  3. Accepted Manuscript published: June 30, 2020 (version 1)

Copyright

© 2020, Kolich 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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