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

Summary CorA, the major Mg 2+ uptake system in prokaryotes, is gated by intracellular Mg 2+ (K D ∼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 A, respectively. In the absence of bound Mg 2+ , four of the five subunits are displaced to variable extents (∼10–25 A) 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.