Real time dynamics of gating-related conformational changes in CorA

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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 K_d, 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.

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

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Martina Rangl

Department of Anesthesiology, Weill Cornell Medical College, New York, United States

Competing interests
The authors declare that no competing interests exist.
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.
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.

"This ORCID iD identifies the author of this article:" 0000-0001-7132-2793
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.

"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.

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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.