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Structure paper

TitleConformational ensembles of the magnesium channel CorA reveal structural basis for channel gating.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 123, Issue 8, Page e2512532123, Year 2026
Publish dateFeb 24, 2026
AuthorsSatchal K Erramilli / Kamil Nosol / Krzysztof Pietrzak-Lichwa / Nicolaus Schmandt / Tian Li / Piotr Tokarz / Jingkai Hou / Minglei Zhao / Eduardo Perozo / Anthony A Kossiakoff /
PubMed AbstractIn 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 linksProc Natl Acad Sci U S A / PubMed:41701836
MethodsEM (single particle)
Resolution3.0 - 4.1 Å
Structure data

EMDB-41384, PDB-8tmc:
Cryo-EM structure of CorA in complex with conformation-specific synthetic antibody C12 and 20 mM MgCl2, State MG20-2
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-41385, PDB-8tmd:
Cryo-EM structure of CorA in complex with conformation-specific synthetic antibody C18 and 100 uM MgCl2, State MG0.1-1A
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-41386, PDB-8tme:
Cryo-EM structure of CorA in complex with conformation-specific synthetic antibody C18 and 100 uM MgCl2, State MG0.1-1B
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-41387, PDB-8tmf:
Cryo-EM structure of CorA in complex with conformation-specific synthetic antibody C18 and 100 uM MgCl2, State MG0.1-1C
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-41388, PDB-8tmg:
Cryo-EM structure of CorA in complex with conformation-specific synthetic antibody C18 and 100 uM MgCl2, State MG0.1-2A
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-41389, PDB-8tmh:
Cryo-EM structure of CorA in complex with conformation-specific synthetic antibody C18 and 100 uM MgCl2, State MG0.1-2B
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-41390, PDB-8tmi:
Cryo-EM structure of CorA in complex with conformation-specific synthetic antibody C18 and 100 uM MgCl2, State MG0.1-2C
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-41391, PDB-8tmj:
Cryo-EM structure of CorA in complex with conformation-specific synthetic antibody C18 and 100 uM MgCl2, State MG0.1-2D
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-41392, PDB-8tmk:
Cryo-EM structure of magnesium depleted CorA in complex with conformation-specific synthetic antibody C18, State MGD-2C
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-41393, PDB-8tml:
Cryo-EM structure of magnesium depleted CorA in complex with conformation-specific synthetic antibody C18, State MGD-2B
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-41394, PDB-8tmm:
Cryo-EM structure of magnesium depleted CorA in complex with conformation-specific synthetic antibody C18, State MGD-2A
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-41395, PDB-8tmn:
Cryo-EM structure of magnesium depleted CorA in complex with conformation-specific synthetic antibody C18, State MGD-1D
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-41396, PDB-8tmo:
Cryo-EM structure of magnesium depleted CorA in complex with conformation-specific synthetic antibody C18, State MGD-1C
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-41397, PDB-8tmp:
Cryo-EM structure of magnesium depleted CorA in complex with conformation-specific synthetic antibody C18, State MGD-1B
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-41398, PDB-8tmq:
Cryo-EM structure of magnesium depleted CorA in complex with conformation-specific synthetic antibody C18, State MGD-1A
Method: EM (single particle) / Resolution: 3.1 Å

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
Method: EM (single particle) / Resolution: 4.1 Å

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
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-41406: Consensus cryo-EM refinement map for magnesium depleted CorA in complex with conformation-specific synthetic antibody C18, State MGD-1D
Method: EM (single particle) / Resolution: 3.3 Å

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
Method: EM (single particle) / Resolution: 4.0 Å

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
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-41414: Consensus cryo-EM refinement map for magnesium depleted CorA in complex with conformation-specific synthetic antibody C18, State MGD-1C
Method: EM (single particle) / Resolution: 3.1 Å

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
Method: EM (single particle) / Resolution: 3.7 Å

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
Method: EM (single particle) / Resolution: 3.7 Å

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
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-MG:
Unknown entry

Source
  • thermotoga maritima (bacteria)
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / Ion Channel / Magnesium Channel

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