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TitleClosed and open structures of the eukaryotic magnesium channel Mrs2 reveal the auto-ligand-gating regulation mechanism.
Journal, issue, pagesNat Struct Mol Biol, Vol. 32, Issue 3, Page 491-501, Year 2025
Publish dateNov 28, 2024
AuthorsPing Li / Shiyan Liu / Johan Wallerstein / Rhiza Lyne E Villones / Peng Huang / Karin Lindkvist-Petersson / Gabriele Meloni / Kefeng Lu / Kristine Steen Jensen / Sara I Liin / Pontus Gourdon /
PubMed AbstractThe CorA/Mrs2 family of pentameric proteins are cardinal for the influx of Mg across cellular membranes, importing the cation to mitochondria in eukaryotes. Yet, the conducting and regulation ...The CorA/Mrs2 family of pentameric proteins are cardinal for the influx of Mg across cellular membranes, importing the cation to mitochondria in eukaryotes. Yet, the conducting and regulation mechanisms of permeation remain elusive, particularly for the eukaryotic Mrs2 members. Here, we report closed and open Mrs2 cryo-electron microscopy structures, accompanied by functional characterization. Mg flux is permitted by a narrow pore, gated by methionine and arginine residues in the closed state. Transition between the conformations is orchestrated by two pairs of conserved sensor-serving Mg-binding sites in the mitochondrial matrix lumen, located in between monomers. At lower levels of Mg, these ions are stripped, permitting an alternative, symmetrical shape, maintained by the RDLR motif that replaces one of the sensor site pairs in the open conformation. Thus, our findings collectively establish the molecular basis for selective Mg influx of Mrs2 and an auto-ligand-gating regulation mechanism.
External linksNat Struct Mol Biol / PubMed:39609652 / PubMed Central
MethodsEM (single particle)
Resolution2.68 - 3.22 Å
Structure data

EMDB-18256, PDB-8q8p:
Cryo-EM structure of the magnesium channel CtMrs2 in the closed state
Method: EM (single particle) / Resolution: 2.68 Å

EMDB-18257, PDB-8q8q:
Cryo-EM structure of the magnesium channel CtMrs2 in the open state
Method: EM (single particle) / Resolution: 3.22 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-LOP:
(1R)-2-{[(R)-(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-1-[(DODECANOYLOXY)METHYL]ETHYL (9Z)-OCTADEC-9-ENOATE / phospholipid*YM

Source
  • thermochaetoides thermophila (fungus)
KeywordsMEMBRANE PROTEIN / Magnesium channel Mrs2

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