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| Title | Conformational ensembles of the magnesium channel CorA reveal structural basis for channel gating. |
|---|---|
| Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 123, Issue 8, Page e2512532123, Year 2026 |
| Publish date | Feb 24, 2026 |
Authors | Satchal K Erramilli / Kamil Nosol / Krzysztof Pietrzak-Lichwa / Nicolaus Schmandt / Tian Li / Piotr Tokarz / Jingkai Hou / Minglei Zhao / Eduardo Perozo / Anthony A Kossiakoff / ![]() |
| PubMed Abstract | In prokaryotes, CorA is the primary influx pathway for magnesium, a critical divalent cation in cellular physiology and biochemistry. Mechanistic studies show that homopentameric CorA is regulated ...In prokaryotes, CorA is the primary influx pathway for magnesium, a critical divalent cation in cellular physiology and biochemistry. Mechanistic studies show that homopentameric CorA is regulated through an intracellular [Mg]-dependent negative feedback loop, involving the asymmetric participation of individual subunits. To understand the connection between asymmetry and activation, we used single-particle cryo-EM to solve sixteen structures of nanodisc-reconstituted CorA. We utilized conformation-specific synthetic antibodies to stabilize subtle but significant conformational differences in the cryo-EM structures. Our results demonstrate that CorA exists as a set of conformational ensembles, where population size inversely correlates with intracellular Mg concentration. These ensembles include channels with a variety of pore conformations, both constricted and dilated, suggesting a spectrum of active CorA functional states. The ensembles connect asymmetric structural transitions in the cytoplasmic domain with conformational changes in the permeation pathway via an electrostatic network, ultimately controlling channel-gating events. We believe that these results establish a framework for understanding magnesium homeostasis in prokaryotic systems. |
External links | Proc Natl Acad Sci U S A / PubMed:41701836 |
| Methods | EM (single particle) |
| Resolution | 3.0 - 4.1 Å |
| Structure data | EMDB-41384, PDB-8tmc: EMDB-41385, PDB-8tmd: EMDB-41386, PDB-8tme: EMDB-41387, PDB-8tmf: EMDB-41388, PDB-8tmg: EMDB-41389, PDB-8tmh: EMDB-41390, PDB-8tmi: EMDB-41391, PDB-8tmj: EMDB-41392, PDB-8tmk: EMDB-41393, PDB-8tml: EMDB-41394, PDB-8tmm: EMDB-41395, PDB-8tmn: EMDB-41396, PDB-8tmo: EMDB-41397, PDB-8tmp: EMDB-41398, PDB-8tmq: ![]() EMDB-41404: Local cryo-EM refinement map (Chain C N-terminal domain) for magnesium depleted CorA in complex with conformation-specific synthetic antibody C18, State MGD-1D ![]() EMDB-41405: Local cryo-EM refinement map (Chain D N-terminal domain) for magnesium depleted CorA in complex with conformation-specific synthetic antibody C18, State MGD-1D ![]() EMDB-41406: Consensus cryo-EM refinement map for magnesium depleted CorA in complex with conformation-specific synthetic antibody C18, State MGD-1D ![]() EMDB-41412: Local cryo-EM refinement map (Chain C N-terminal domain) for magnesium depleted CorA in complex with conformation-specific synthetic antibody C18, State MGD-1C ![]() EMDB-41413: Local cryo-EM refinement map (Chain D N-terminal domain) for magnesium depleted CorA in complex with conformation-specific synthetic antibody C18, State MGD-1C ![]() EMDB-41414: Consensus cryo-EM refinement map for magnesium depleted CorA in complex with conformation-specific synthetic antibody C18, State MGD-1C ![]() EMDB-41419: Local cryo-EM refinement map (Chain D N-terminal domain) for CorA in complex with conformation-specific synthetic antibody C18 and 100 uM MgCl2, State MG0.1-1B ![]() EMDB-41420: Local cryo-EM refinement map (Chain C N-terminal domain) for CorA in complex with conformation-specific synthetic antibody C18 and 100 uM MgCl2, State MG0.1-1B ![]() EMDB-41421: Consensus cryo-EM refinement map for CorA in complex with conformation-specific synthetic antibody C18 and 100 uM MgCl2, State MG0.1-1B |
| Chemicals | ![]() ChemComp-MG: |
| Source |
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Keywords | MEMBRANE PROTEIN / Ion Channel / Magnesium Channel |
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