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TitleStructure and mechanism of the mitochondrial Ca uniporter holocomplex.
Journal, issue, pagesNature, Vol. 582, Issue 7810, Page 129-133, Year 2020
Publish dateMay 20, 2020
AuthorsMinrui Fan / Jinru Zhang / Chen-Wei Tsai / Benjamin J Orlando / Madison Rodriguez / Yan Xu / Maofu Liao / Ming-Feng Tsai / Liang Feng /
PubMed AbstractMitochondria take up Ca through the mitochondrial calcium uniporter complex to regulate energy production, cytosolic Ca signalling and cell death. In mammals, the uniporter complex (uniplex) contains ...Mitochondria take up Ca through the mitochondrial calcium uniporter complex to regulate energy production, cytosolic Ca signalling and cell death. In mammals, the uniporter complex (uniplex) contains four core components: the pore-forming MCU protein, the gatekeepers MICU1 and MICU2, and an auxiliary subunit, EMRE, essential for Ca transport. To prevent detrimental Ca overload, the activity of MCU must be tightly regulated by MICUs, which sense changes in cytosolic Ca concentrations to switch MCU on and off. Here we report cryo-electron microscopic structures of the human mitochondrial calcium uniporter holocomplex in inhibited and Ca-activated states. These structures define the architecture of this multicomponent Ca-uptake machinery and reveal the gating mechanism by which MICUs control uniporter activity. Our work provides a framework for understanding regulated Ca uptake in mitochondria, and could suggest ways of modulating uniporter activity to treat diseases related to mitochondrial Ca overload.
External linksNature / PubMed:32494073 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 3.6 Å
Structure data

21642

6wdn

EMDB-21642, PDB-6wdn:
Cryo-EM structure of mitochondrial calcium uniporter holocomplex in low Ca2+
Method: EM (single particle) / Resolution: 3.2 Å

21643

6wdo

EMDB-21643, PDB-6wdo:
Cryo-EM structure of mitochondrial calcium uniporter holocomplex in high Ca2+
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-CA:
Unknown entry

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN

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