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Structure paper

TitleX-ray and cryo-EM structures of the mitochondrial calcium uniporter.
Journal, issue, pagesNature, Vol. 559, Issue 7715, Page 575-579, Year 2018
Publish dateJul 11, 2018
AuthorsChao Fan / Minrui Fan / Benjamin J Orlando / Nathan M Fastman / Jinru Zhang / Yan Xu / Melissa G Chambers / Xiaofang Xu / Kay Perry / Maofu Liao / Liang Feng /
PubMed AbstractMitochondrial calcium uptake is critical for regulating ATP production, intracellular calcium signalling, and cell death. This uptake is mediated by a highly selective calcium channel called the ...Mitochondrial calcium uptake is critical for regulating ATP production, intracellular calcium signalling, and cell death. This uptake is mediated by a highly selective calcium channel called the mitochondrial calcium uniporter (MCU). Here, we determined the structures of the pore-forming MCU proteins from two fungi by X-ray crystallography and single-particle cryo-electron microscopy. The stoichiometry, overall architecture, and individual subunit structure differed markedly from those described in the recent nuclear magnetic resonance structure of Caenorhabditis elegans MCU. We observed a dimer-of-dimer architecture across species and chemical environments, which was corroborated by biochemical experiments. Structural analyses and functional characterization uncovered the roles of key residues in the pore. These results reveal a new ion channel architecture, provide insights into calcium coordination, selectivity and conduction, and establish a structural framework for understanding the mechanism of mitochondrial calcium uniporter function.
External linksNature / PubMed:29995856 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution3.09608311048 - 7.0 Å
Structure data

EMDB-7800:
Cryo-EM map of F.graminearum Mitochondrial Calcium Uniporter in lipid nanodisc - overall
Method: EM (single particle) / Resolution: 4.9 Å

EMDB-7801:
Cryo-EM map of F.graminearum Mitochondrial Calcium Uniporter in lipid nanodisc - type 1
Method: EM (single particle) / Resolution: 4.9 Å

EMDB-7802:
Cryo-EM map of F.graminearum Mitochondrial Calcium Uniporter in lipid nanodisc - type 2
Method: EM (single particle) / Resolution: 4.9 Å

EMDB-7803:
Cryo-EM map of F.graminearum Mitochondrial Calcium Uniporter in PMAL-C8
Method: EM (single particle) / Resolution: 5.0 Å

EMDB-7804:
Cryo-EM map of M.acridum Mitochondrial Calcium Uniporter in A8-35 amphipol
Method: EM (single particle) / Resolution: 7.0 Å

PDB-6c5r:
Crystal structure of the soluble domain of the mitochondrial calcium uniporter
Method: X-RAY DIFFRACTION / Resolution: 3.09608311048 Å

PDB-6c5w:
Crystal structure of the mitochondrial calcium uniporter
Method: X-RAY DIFFRACTION / Resolution: 3.10010233314 Å

Chemicals

ChemComp-CA:
Unknown entry

Source
  • Fusarium graminearum (fungus)
  • Metarhizium acridum (fungus)
  • metarhizium acridum (strain cqma 102) (fungus)
  • unknown (others)
KeywordsCYTOSOLIC PROTEIN / MEMBRANE PROTEIN

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