Department of Anesthesiology

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Real time dynamics of gating-related conformational changes in CorA.

TitleReal time dynamics of gating-related conformational changes in CorA.
Publication TypeJournal Article
Year of Publication2019
AuthorsRangl M, Schmandt N, Perozo E, Scheuring S
JournalElife
Volume8
Date Published2019 Nov 27
ISSN2050-084X
Abstract

CorA, a divalent-selective channel in the metal ion transport superfamily, is the major Mg-influx pathway in prokaryotes. CorA structures in closed (Mg-bound), and open (Mg-free) states, together with functional data showed that Mg-influx inhibits further Mg-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 Mg-dependent gating transition of single CorA channels: HS-AFM movies during Mg-depletion experiments revealed the channel's transition from a stable Mg-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 Mg-concentration below K, 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.

DOI10.7554/eLife.47322
Alternate JournalElife
PubMed ID31774394
Grant ListR01GM120561 / NH / NIH HHS / United States
R01GM124451 / NH / NIH HHS / United States