title: Cryo-EM Structures of the Magnesium Channel CorA Reveal Symmetry Break upon Gating.
abstract: CorA, the major Mg(2+) uptake system in prokaryotes, is gated by intracellular Mg(2+) (KD ∼ 1-2 mM). X-ray crystallographic studies of CorA show similar conformations under Mg(2+)-bound and Mg(2+)-free conditions, but EPR spectroscopic studies reveal large Mg(2+)-driven quaternary conformational changes. Here, we determined cryo-EM structures of CorA in the Mg(2+)-bound closed conformation and in two open Mg(2+)-free states at resolutions of 3.8, 7.1, and 7.1 Å, respectively. In the absence of bound Mg(2+), four of the five subunits are displaced to variable extents (∼ 10-25 Å) by hinge-like motions as large as ∼ 35° at the stalk helix. The transition between a single 5-fold symmetric closed state and an ensemble of low Mg(2+), open, asymmetric conformational states is, thus, the key structural signature of CorA gating. This mechanism is likely to apply to other structurally similar divalent ion channels.
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Doreen
authors.initials: D
authors.lastname: Matthies
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Dalmas
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Mario J
authors.initials: MJ
authors.lastname: Borgnia
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Pawel K
authors.initials: PK
authors.lastname: Dominik
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Merk
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Prashant
authors.initials: P
authors.lastname: Rao
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Bharat G
authors.initials: BG
authors.lastname: Reddy
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Shahidul
authors.initials: S
authors.lastname: Islam
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bartesaghi
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. Electronic address: eperozo@uchicago.edu.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Perozo
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: ss1@nih.gov.
authors.forename: Sriram
authors.initials: S
authors.lastname: Subramaniam
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000648:ultrastructure*; D027682:Cation Transport Proteins / Q000737:chemistry / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D008274:Magnesium / Q000378:metabolism*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D020124:Thermotoga maritima / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D008274:Magnesium
keywords: asymmetry; conformational change; direct electron detector; ion channel; membrane protein structure; single-particle cryo-electron microscopy