6WDN

Cryo-EM structure of mitochondrial calcium uniporter holocomplex in low Ca2+

Summary for 6WDN

• Entry DOI: 10.2210/pdb6wdn/pdb
• EMDB information: 21642
• Descriptor: Calcium uptake protein 2, mitochondrial, Calcium uptake protein 1, mitochondrial, Essential MCU regulator, mitochondrial, ... (4 entities in total)
• Functional Keywords: membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 189353.89

Authors

Feng, L.,Zhang, J.,Fan, M. (deposition date: 2020-04-01, release date: 2020-05-27, Last modification date: 2024-11-06)

Primary citation

Fan, M.,Zhang, J.,Tsai, C.W.,Orlando, B.J.,Rodriguez, M.,Xu, Y.,Liao, M.,Tsai, M.F.,Feng, L.
Structure and mechanism of the mitochondrial Ca2+uniporter holocomplex.
Nature, 582:129-133, 2020

PubMed Abstract: 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.

PubMed: 32494073
DOI: 10.1038/s41586-020-2309-6

Experimental method

ELECTRON MICROSCOPY (3.2 Å)