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Closed and open structures of the eukaryotic magnesium channel Mrs2 reveal the auto-ligand-gating regulation mechanism

Li, Ping LU ; Liu, Shiyan ; Wallerstein, Johan LU orcid ; Villones, Rhiza Lyne E. ; Huang, Peng LU ; Lindkvist-Petersson, Karin LU ; Meloni, Gabriele ; Lu, Kefeng ; Steen Jensen, Kristine LU and Liin, Sara I. , et al. (2024) In Nature Structural and Molecular Biology
Abstract

The CorA/Mrs2 family of pentameric proteins are cardinal for the influx of Mg2+ across cellular membranes, importing the cation to mitochondria in eukaryotes. Yet, the conducting and regulation mechanisms of permeation remain elusive, particularly for the eukaryotic Mrs2 members. Here, we report closed and open Mrs2 cryo-electron microscopy structures, accompanied by functional characterization. Mg2+ flux is permitted by a narrow pore, gated by methionine and arginine residues in the closed state. Transition between the conformations is orchestrated by two pairs of conserved sensor-serving Mg2+-binding sites in the mitochondrial matrix lumen, located in between monomers. At lower levels of... (More)

The CorA/Mrs2 family of pentameric proteins are cardinal for the influx of Mg2+ across cellular membranes, importing the cation to mitochondria in eukaryotes. Yet, the conducting and regulation mechanisms of permeation remain elusive, particularly for the eukaryotic Mrs2 members. Here, we report closed and open Mrs2 cryo-electron microscopy structures, accompanied by functional characterization. Mg2+ flux is permitted by a narrow pore, gated by methionine and arginine residues in the closed state. Transition between the conformations is orchestrated by two pairs of conserved sensor-serving Mg2+-binding sites in the mitochondrial matrix lumen, located in between monomers. At lower levels of Mg2+, these ions are stripped, permitting an alternative, symmetrical shape, maintained by the RDLR motif that replaces one of the sensor site pairs in the open conformation. Thus, our findings collectively establish the molecular basis for selective Mg2+ influx of Mrs2 and an auto-ligand-gating regulation mechanism.

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Contribution to journal
publication status
in press
subject
in
Nature Structural and Molecular Biology
publisher
Nature Publishing Group
external identifiers
  • pmid:39609652
  • scopus:85210485440
ISSN
1545-9993
DOI
10.1038/s41594-024-01432-1
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2024.
id
ba69a286-a91d-4b7f-921d-19a3de879309
date added to LUP
2025-01-15 13:27:40
date last changed
2025-07-03 03:44:11
@article{ba69a286-a91d-4b7f-921d-19a3de879309,
  abstract     = {{<p>The CorA/Mrs2 family of pentameric proteins are cardinal for the influx of Mg<sup>2+</sup> across cellular membranes, importing the cation to mitochondria in eukaryotes. Yet, the conducting and regulation mechanisms of permeation remain elusive, particularly for the eukaryotic Mrs2 members. Here, we report closed and open Mrs2 cryo-electron microscopy structures, accompanied by functional characterization. Mg<sup>2+</sup> flux is permitted by a narrow pore, gated by methionine and arginine residues in the closed state. Transition between the conformations is orchestrated by two pairs of conserved sensor-serving Mg<sup>2+</sup>-binding sites in the mitochondrial matrix lumen, located in between monomers. At lower levels of Mg<sup>2+</sup>, these ions are stripped, permitting an alternative, symmetrical shape, maintained by the RDLR motif that replaces one of the sensor site pairs in the open conformation. Thus, our findings collectively establish the molecular basis for selective Mg<sup>2+</sup> influx of Mrs2 and an auto-ligand-gating regulation mechanism.</p>}},
  author       = {{Li, Ping and Liu, Shiyan and Wallerstein, Johan and Villones, Rhiza Lyne E. and Huang, Peng and Lindkvist-Petersson, Karin and Meloni, Gabriele and Lu, Kefeng and Steen Jensen, Kristine and Liin, Sara I. and Gourdon, Pontus}},
  issn         = {{1545-9993}},
  language     = {{eng}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Structural and Molecular Biology}},
  title        = {{Closed and open structures of the eukaryotic magnesium channel Mrs2 reveal the auto-ligand-gating regulation mechanism}},
  url          = {{http://dx.doi.org/10.1038/s41594-024-01432-1}},
  doi          = {{10.1038/s41594-024-01432-1}},
  year         = {{2024}},
}