Molecular basis of Mg²⁺ permeation through the human mitochondrial Mrs2 channel.

ABSTRACT: Mitochondrial RNA splicing 2 (Mrs2), a eukaryotic CorA ortholog, enables Mg²⁺ to permeate the inner mitochondrial membrane and plays an important role in mitochondrial metabolic function. However, the mechanism by which Mrs2 permeates Mg²⁺ 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 Mg²⁺ uptake assays show that the R-ring may function as a charge repulsion barrier, and

SUBMITTER: Li M 

PROVIDER: S-EPMC10404273 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature