6LB8

Crystal structure of the Ca2+-free T4L-MICU1-MICU2 complex

6LB8 の概要

• エントリーDOI: 10.2210/pdb6lb8/pdb
• 分子名称: Endolysin,Calcium uptake protein 1, mitochondrial, Calcium uptake protein 2, mitochondrial (2 entities in total)
• 機能のキーワード: calcium binding protein, mitochondrial, uniporter, ef-hand, metal binding protein
• 由来する生物種: Escherichia virus T4; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 198081.89

構造登録者

Wu, W.,Shen, Q.,Zheng, J.,Jia, Z. (登録日: 2019-11-13, 公開日: 2020-07-15, 最終更新日: 2023-11-22)

主引用文献

Wu, W.,Shen, Q.,Zhang, R.,Qiu, Z.,Wang, Y.,Zheng, J.,Jia, Z.
The structure of the MICU1-MICU2 complex unveils the regulation of the mitochondrial calcium uniporter.
Embo J., 39:e104285-e104285, 2020

PubMed Abstract: The MICU1-MICU2 heterodimer regulates the mitochondrial calcium uniporter (MCU) and mitochondrial calcium uptake. Herein, we present two crystal structures of the MICU1-MICU2 heterodimer, in which Ca -free and Ca -bound EF-hands are observed in both proteins, revealing both electrostatic and hydrophobic interfaces. Furthermore, we show that MICU1 interacts with EMRE, another regulator of MCU, through a Ca -dependent alkaline groove. Ca binding strengthens the MICU1-EMRE interaction, which in turn facilitates Ca uptake. Conversely, the MICU1-MCU interaction is favored in the absence of Ca , thus inhibiting the channel activity. This Ca -dependent switch illuminates how calcium signals are transmitted from regulatory subunits to the calcium channel and the transition between gatekeeping and activation channel functions. Furthermore, competition with an EMRE peptide alters the uniporter threshold in resting conditions and elevates Ca accumulation in stimulated mitochondria, confirming the gatekeeper role of the MICU1-MICU2 heterodimer. Taken together, these structural and functional data provide new insights into the regulation of mitochondrial calcium uptake.

PubMed: 32790952
DOI: 10.15252/embj.2019104285

実験手法

X-RAY DIFFRACTION (3.283 Å)