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TitleMolecular basis of Mg permeation through the human mitochondrial Mrs2 channel.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 4713, Year 2023
Publish dateAug 5, 2023
AuthorsMing Li / Yang Li / Yue Lu / Jianhui Li / Xuhang Lu / Yue Ren / Tianlei Wen / Yaojie Wang / Shenghai Chang / Xing Zhang / Xue Yang / Yuequan Shen /
PubMed AbstractMitochondrial RNA splicing 2 (Mrs2), a eukaryotic CorA ortholog, enables Mg to permeate the inner mitochondrial membrane and plays an important role in mitochondrial metabolic function. However, the ...Mitochondrial RNA splicing 2 (Mrs2), a eukaryotic CorA ortholog, enables Mg to permeate the inner mitochondrial membrane and plays an important role in mitochondrial metabolic function. However, the mechanism by which Mrs2 permeates Mg remains unclear. Here, we report four cryo-electron microscopy (cryo-EM) reconstructions of Homo sapiens Mrs2 (hMrs2) under various conditions. All of these hMrs2 structures form symmetrical pentamers with very similar pentamer and protomer conformations. A special structural feature of Cl-bound R-ring, which consists of five Arg332 residues, was found in the hMrs2 structure. Molecular dynamics simulations and mitochondrial Mg uptake assays show that the R-ring may function as a charge repulsion barrier, and Cl may function as a ferry to jointly gate Mg permeation in hMrs2. In addition, the membrane potential is likely to be the driving force for Mg permeation. Our results provide insights into the channel assembly and Mg permeation of hMrs2.
External linksNat Commun / PubMed:37543649 / PubMed Central
MethodsEM (single particle)
Resolution2.5 - 2.9 Å
Structure data

35630

8ip3

EMDB-35630, PDB-8ip3:
Cryo-EM structure of hMRS2-Mg
Method: EM (single particle) / Resolution: 2.6 Å

35631

8ip4

EMDB-35631, PDB-8ip4:
Cryo-EM structure of hMRS-highEDTA
Method: EM (single particle) / Resolution: 2.7 Å

35632

8ip5

EMDB-35632, PDB-8ip5:
Cryo-EM structure of hMRS2-lowEDTA
Method: EM (single particle) / Resolution: 2.5 Å

35633

8ip6

EMDB-35633, PDB-8ip6:
Cryo-EM structure of hMRS2-rest
Method: EM (single particle) / Resolution: 2.9 Å

Chemicals

ChemComp-CL:
Unknown entry / Chloride

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
KeywordsMETAL TRANSPORT / pentamer

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