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-Structure paper
| タイトル | Structure and function of the human mitochondrial MRS2 channel. |
|---|---|
| ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 32, Issue 3, Page 459-468, Year 2025 |
| 掲載日 | 2024年11月28日 |
著者 | Zhihui He / Yung-Chi Tu / Chen-Wei Tsai / Jonathan Mount / Jingying Zhang / Ming-Feng Tsai / Peng Yuan / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nat Struct Mol Biol / PubMed:39609651 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.92 - 3.11 Å |
| 構造データ | EMDB-41587, PDB-8ts1: EMDB-41588, PDB-8ts2: EMDB-41589, PDB-8ts3: |
| 化合物 | ![]() ChemComp-MG: ![]() ChemComp-CA: |
| 由来 |
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キーワード | METAL TRANSPORT / mitochondria / pentamer / cation channel |
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homo sapiens (ヒト)
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