1. Structural Biology and Molecular Biophysics
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Real time dynamics of gating-related conformational changes in CorA

  1. Martina Rangl
  2. Nicolaus Schmandt
  3. Eduardo Perozo  Is a corresponding author
  4. Simon Scheuring  Is a corresponding author
  1. Weill Cornell Medical College, United States
  2. The University of Chicago, United States
Research Article
  • Cited 1
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Cite this article as: eLife 2019;8:e47322 doi: 10.7554/eLife.47322

Abstract

CorA, a divalent-selective channel in the metal ion transport superfamily, is the major Mg2+-influx pathway in prokaryotes. CorA structures in closed (Mg2+-bound), and open (Mg2+-free) states, together with functional data showed that Mg2+-influx inhibits further Mg2+-uptake completing a regulatory feedback loop. While the closed state structure is a symmetric pentamer, the open state displayed unexpected asymmetric architectures. Using high-speed atomic force microscopy (HS-AFM), we explored the Mg2+-dependent gating transition of single CorA channels: HS-AFM movies during Mg2+-depletion experiments revealed the channel's transition from a stable Mg2+-bound state over a highly mobile and dynamic state with fluctuating subunits to asymmetric structures with varying degree of protrusion heights from the membrane. Our data shows that at Mg2+-concentration below Kd, CorA adopts a dynamic (putatively open) state of multiple conformations that imply structural rearrangements through hinge-bending in TM1. We discuss how these structural dynamics define the functional behavior of this ligand-dependent channel.

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. Martina Rangl

    Department of Anesthesiology, Weill Cornell Medical College, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Nicolaus Schmandt

    Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Eduardo Perozo

    Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States
    For correspondence
    eperozo@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7132-2793
  4. Simon Scheuring

    Department of Anesthesiology, Weill Cornell Medical College, New York, United States
    For correspondence
    sis2019@med.cornell.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3534-069X

Funding

National Institutes of Health (R01GM120561)

  • Eduardo Perozo

National Institutes of Health (R01GM124451)

  • Simon Scheuring

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

Reviewing Editor

  1. Baron Chanda, University of Wisconsin-Madison, United States

Publication history

  1. Received: April 1, 2019
  2. Accepted: November 26, 2019
  3. Accepted Manuscript published: November 27, 2019 (version 1)
  4. Version of Record published: December 23, 2019 (version 2)

Copyright

© 2019, Rangl 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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