8IP3

Cryo-EM structure of hMRS2-Mg

Summary for 8IP3

• Entry DOI: 10.2210/pdb8ip3/pdb
• EMDB information: 35630
• Descriptor: Magnesium transporter MRS2 homolog, mitochondrial, CHLORIDE ION, MAGNESIUM ION (3 entities in total)
• Functional Keywords: pentamer, metal transport
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 5
• Total formula weight: 257985.47

Authors

Li, M.,Li, Y.,Yang, X.,Shen, Y.Q. (deposition date: 2023-03-14, release date: 2023-06-14, Last modification date: 2023-08-30)

Primary citation

Li, M.,Li, Y.,Lu, Y.,Li, J.,Lu, X.,Ren, Y.,Wen, T.,Wang, Y.,Chang, S.,Zhang, X.,Yang, X.,Shen, Y.
Molecular basis of Mg 2+ permeation through the human mitochondrial Mrs2 channel.
Nat Commun, 14:4713-4713, 2023

PubMed Abstract: 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.

PubMed: 37543649
DOI: 10.1038/s41467-023-40516-2

Experimental method

ELECTRON MICROSCOPY (2.6 Å)