6AGI

Crystal Structure of EFHA2 in Ca-binding State

6AGI の概要

• エントリーDOI: 10.2210/pdb6agi/pdb
• 分子名称: Calcium uptake protein 3, mitochondrial, CALCIUM ION, IMIDAZOLE, ... (4 entities in total)
• 機能のキーワード: mitochondrial, calcium, calcium binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 89742.73

構造登録者

Yangfei, X.,Xue, Y.,Yuequan, S. (登録日: 2018-08-11, 公開日: 2019-01-23, 最終更新日: 2023-11-22)

主引用文献

Xing, Y.,Wang, M.,Wang, J.,Nie, Z.,Wu, G.,Yang, X.,Shen, Y.
Dimerization of MICU Proteins Controls Ca2+Influx through the Mitochondrial Ca2+Uniporter.
Cell Rep, 26:1203-1212.e4, 2019

PubMed Abstract: The mitochondrial Ca uniporter complex (MCUC) is responsible for Ca influx into the mitochondrial matrix, playing critical roles in various mitochondrial functions. Eukaryotic MCUC consists of multiple subunits, and its Ca influx activity is controlled by regulatory subunits, including mitochondrial Ca uptake 1 (MICU1) and its paralogs (MICU2 and MICU3). However, the underlying mechanism remains unclear. Here, we determined multiple crystal structures of MICU2 and MICU3 from Homo sapiens. Our data demonstrate that distinct MICU protein N-domains determine the specific type of MICU dimers that perform the opposing roles in mitochondrial Ca uptake at low cytosolic Ca levels. In contrast, at high cytosolic Ca levels, all MICU proteins undergo dimer rearrangement induced by Ca binding, which releases the suppression of the MCUC pore-forming subunit and promotes the influx of large amounts of Ca. Altogether, our results elucidate the delicate mechanism of mitochondrial Ca uptake regulation by MICU proteins.

PubMed: 30699349
DOI: 10.1016/j.celrep.2019.01.022

実験手法

X-RAY DIFFRACTION (2.799 Å)