8TS2

Cryo-EM structure of human MRS2 with EDTA

8TS2 の概要

• エントリーDOI: 10.2210/pdb8ts2/pdb
• EMDBエントリー: 41587 41588
• 分子名称: Magnesium transporter MRS2 homolog, mitochondrial, Soluble cytochrome b562 fusion protein (1 entity in total)
• 機能のキーワード: mitochondria, pentamer, cation channel, metal transport
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 277358.46

構造登録者

He, Z.,Mount, J.W.,Zhang, J.,Yuan, P. (登録日: 2023-08-10, 公開日: 2024-08-14, 最終更新日: 2025-04-02)

主引用文献

He, Z.,Tu, Y.C.,Tsai, C.W.,Mount, J.,Zhang, J.,Tsai, M.F.,Yuan, P.
Structure and function of the human mitochondrial MRS2 channel.
Nat.Struct.Mol.Biol., 32:459-468, 2025

PubMed Abstract: The human mitochondrial RNA splicing 2 protein (MRS2) has been implicated in Mg transport across mitochondrial inner membranes, thus having an important role in Mg homeostasis critical for mitochondrial integrity and function. However, the molecular mechanisms underlying its fundamental channel properties such as ion selectivity and regulation remain unclear. Here we present a structural and functional investigation of MRS2. Cryo-electron microscopy structures in various ionic conditions reveal a pentameric channel architecture and the molecular basis of ion permeation and potential regulation mechanisms. Electrophysiological analyses demonstrate that MRS2 is a Ca-regulated, nonselective channel permeable to Mg, Ca, Na and K, which contrasts with its prokaryotic ortholog, CorA, operating as a Mg-gated Mg channel. Moreover, a conserved arginine ring within the pore of MRS2 functions to restrict cation movements, thus preventing the channel from collapsing the proton motive force that drives mitochondrial adenosine triphosphate synthesis. Together, our results provide a molecular framework for further understanding MRS2 in mitochondrial function and disease.

PubMed: 39609651
DOI: 10.1038/s41594-024-01420-5

実験手法

ELECTRON MICROSCOPY (2.95 Å)