Cell
Volume 164, Issue 4, 11 February 2016, Pages 747-756
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Article
Cryo-EM Structures of the Magnesium Channel CorA Reveal Symmetry Break upon Gating

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Highlights

  • Find 3.8 Å resolution cryo-EM structure of the ∼200 kDa magnesium channel CorA

  • Mg2+-free CorA exhibits dramatic loss of symmetry in the cytoplasmic domain

  • Identify two discrete, asymmetric conformations of Mg2+-free CorA

  • Inter-subunit Mg2+ is important for stabilizing the closed state of CorA

Summary

CorA, the major Mg2+ uptake system in prokaryotes, is gated by intracellular Mg2+ (KD ∼1–2 mM). X-ray crystallographic studies of CorA show similar conformations under Mg2+-bound and Mg2+-free conditions, but EPR spectroscopic studies reveal large Mg2+-driven quaternary conformational changes. Here, we determined cryo-EM structures of CorA in the Mg2+-bound closed conformation and in two open Mg2+-free states at resolutions of 3.8, 7.1, and 7.1 Å, respectively. In the absence of bound Mg2+, 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 Mg2+, 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.

Keywords

asymmetry
conformational change
direct electron detector
ion channel
membrane protein structure
single-particle cryo-electron microscopy

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