4XTB

Crystal structure of the N-terminal domain of the human mitochondrial calcium uniporter

4XTB の概要

• エントリーDOI: 10.2210/pdb4xtb/pdb
• 関連するPDBエントリー: 4XSJ
• 分子名称: Calcium uniporter protein, mitochondrial, TETRAETHYLENE GLYCOL (3 entities in total)
• 機能のキーワード: calcium channel, membrane protein, mitochondria, transport protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Mitochondrion inner membrane ; Multi-pass membrane protein : Q8NE86
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14279.37

構造登録者

Lee, Y.,Min, C.K.,Kim, T.G.,Song, H.K.,Lim, Y.,Kim, D.,Shin, K.,Kang, M.,Kang, J.Y.,Youn, H.-S.,Lee, J.-G.,An, J.Y.,Park, K.R.,Lim, J.J.,Kim, J.H.,Kim, J.H.,Park, Z.Y.,Kim, Y.-S.,Wang, J.,Kim, D.H.,Eom, S.H. (登録日: 2015-01-23, 公開日: 2015-09-16, 最終更新日: 2023-11-08)

主引用文献

Lee, Y.,Min, C.K.,Kim, T.G.,Song, H.K.,Lim, Y.,Kim, D.,Shin, K.,Kang, M.,Kang, J.Y.,Youn, H.S.,Lee, J.G.,An, J.Y.,Park, K.R.,Lim, J.J.,Kim, J.H.,Kim, J.H.,Park, Z.Y.,Kim, Y.S.,Wang, J.,Kim, D.H.,Eom, S.H.
Structure and function of the N-terminal domain of the human mitochondrial calcium uniporter.
Embo Rep., 16:1318-1333, 2015

PubMed Abstract: The mitochondrial calcium uniporter (MCU) is responsible for mitochondrial calcium uptake and homeostasis. It is also a target for the regulation of cellular anti-/pro-apoptosis and necrosis by several oncogenes and tumour suppressors. Herein, we report the crystal structure of the MCU N-terminal domain (NTD) at a resolution of 1.50 Å in a novel fold and the S92A MCU mutant at 2.75 Å resolution; the residue S92 is a predicted CaMKII phosphorylation site. The assembly of the mitochondrial calcium uniporter complex (uniplex) and the interaction with the MCU regulators such as the mitochondrial calcium uptake-1 and mitochondrial calcium uptake-2 proteins (MICU1 and MICU2) are not affected by the deletion of MCU NTD. However, the expression of the S92A mutant or a NTD deletion mutant failed to restore mitochondrial Ca(2+) uptake in a stable MCU knockdown HeLa cell line and exerted dominant-negative effects in the wild-type MCU-expressing cell line. These results suggest that the NTD of MCU is essential for the modulation of MCU function, although it does not affect the uniplex formation.

PubMed: 26341627
DOI: 10.15252/embr.201540436

実験手法

X-RAY DIFFRACTION (1.5 Å)