- EMDB-41587: Cryo-EM structure of human MRS2 with Mg2+ -
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Entry
Database: EMDB / ID: EMD-41587
Title
Cryo-EM structure of human MRS2 with Mg2+
Map data
Sample
Complex: hMRS2-BRIL with Mg2+
Protein or peptide: Magnesium transporter MRS2 homolog, mitochondrial, Soluble cytochrome b562 fusion protein
Ligand: MAGNESIUM ION
Keywords
mitochondria / pentamer / cation channel / METAL TRANSPORT
Function / homology
Function and homology information
mitochondrial magnesium ion transmembrane transport / Miscellaneous transport and binding events / magnesium ion transmembrane transporter activity / lactate metabolic process / electron transport chain / transmembrane transport / electron transfer activity / mitochondrial inner membrane / periplasmic space / iron ion binding ...mitochondrial magnesium ion transmembrane transport / Miscellaneous transport and binding events / magnesium ion transmembrane transporter activity / lactate metabolic process / electron transport chain / transmembrane transport / electron transfer activity / mitochondrial inner membrane / periplasmic space / iron ion binding / heme binding / mitochondrion Similarity search - Function
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
R01NS109307
United States
Citation
Journal: Nat Struct Mol Biol / Year: 2025 Title: Structure and function of the human mitochondrial MRS2 channel. Authors: Zhihui He / Yung-Chi Tu / Chen-Wei Tsai / Jonathan Mount / Jingying Zhang / Ming-Feng Tsai / Peng Yuan / 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 ...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.
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