Cryo-EM Structures of the Magnesium Channel CorA Reveal Symmetry Break upon Gating

CorA, the major Mg2+ uptake system in prokaryotes, is gated by intracellular Mg2+ (K-D similar to 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 angstrom, respectively. In the absence of bound Mg2+, four of the five subunits are displaced to variable extents (similar to 10-25 angstrom) by hinge-like motions as large as similar to 35 degrees 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.