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TitleStructure and function of the human mitochondrial MRS2 channel.
Journal, issue, pagesNat Struct Mol Biol, Vol. 32, Issue 3, Page 459-468, Year 2025
Publish dateNov 28, 2024
AuthorsZhihui He / Yung-Chi Tu / Chen-Wei Tsai / Jonathan Mount / Jingying Zhang / Ming-Feng Tsai / Peng Yuan /
PubMed AbstractThe 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.
External linksNat Struct Mol Biol / PubMed:39609651 / PubMed Central
MethodsEM (single particle)
Resolution2.92 - 3.11 Å
Structure data

EMDB-41587, PDB-8ts1:
Cryo-EM structure of human MRS2 with Mg2+
Method: EM (single particle) / Resolution: 2.92 Å

EMDB-41588, PDB-8ts2:
Cryo-EM structure of human MRS2 with EDTA
Method: EM (single particle) / Resolution: 2.95 Å

EMDB-41589, PDB-8ts3:
Cryo-EM structure of human MRS2 with Ca2+
Method: EM (single particle) / Resolution: 3.11 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-CA:
Unknown entry

Source
  • homo sapiens (human)
  • escherichia coli (E. coli)
KeywordsMETAL TRANSPORT / mitochondria / pentamer / cation channel

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