6WDN

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

6WDN の概要

• エントリーDOI: 10.2210/pdb6wdn/pdb
• EMDBエントリー: 21642
• 分子名称: Calcium uptake protein 2, mitochondrial, Calcium uptake protein 1, mitochondrial, Essential MCU regulator, mitochondrial, ... (4 entities in total)
• 機能のキーワード: membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 189353.89

構造登録者

Feng, L.,Zhang, J.,Fan, M. (登録日: 2020-04-01, 公開日: 2020-05-27, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.2 Å)