Cryo-EM Structures of the Magnesium Channel CorA Reveal Symmetry Break upon Gating
Magnesium ions (Mg2+) play essential roles in all living organisms. Bacteria and other prokaryotes rely upon the Mg2+-dependent channel CorA, which is composed of five identical subunits (A-E), to obtain these ions from their surroundings. Studies of CorA showed that, in contrast to most ligand-gated ion channels, binding of Mg2+ leads to channel closure while loss of Mg2+ promotes its opening, suggesting CorA has a unique mechanism of action.
– 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.
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.