2N3Y

NMR structure of the Y48pCMF variant of human cytochrome c in its reduced state

2N3Y の概要

• エントリーDOI: 10.2210/pdb2n3y/pdb
• NMR情報: BMRB: 25660
• 分子名称: Cytochrome c, Mesoheme (2 entities in total)
• 機能のキーワード: cytochrome c, hemeprotein, mitochondria, apoptosis, phosphorylation, electron transport
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion intermembrane space: P99999
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12303.14

構造登録者

Moreno-Beltran, B.,Del Conte, R.,Diaz-Quintana, A.,De la Rosa, M.A.,Turano, P.,Diaz-Moreno, I. (登録日: 2015-06-15, 公開日: 2016-12-14, 最終更新日: 2024-10-30)

主引用文献

Moreno-Beltran, B.,Guerra-Castellano, A.,Diaz-Quintana, A.,Del Conte, R.,Garcia-Maurino, S.M.,Diaz-Moreno, S.,Gonzalez-Arzola, K.,Santos-Ocana, C.,Velazquez-Campoy, A.,De la Rosa, M.A.,Turano, P.,Diaz-Moreno, I.
Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48.
Proc. Natl. Acad. Sci. U.S.A., 114:E3041-E3050, 2017

PubMed Abstract: Regulation of mitochondrial activity allows cells to adapt to changing conditions and to control oxidative stress, and its dysfunction can lead to hypoxia-dependent pathologies such as ischemia and cancer. Although cytochrome phosphorylation-in particular, at tyrosine 48-is a key modulator of mitochondrial signaling, its action and molecular basis remain unknown. Here we mimic phosphorylation of cytochrome by replacing tyrosine 48 with -carboxy-methyl-l-phenylalanine (CMF). The NMR structure of the resulting mutant reveals significant conformational shifts and enhanced dynamics around CMF that could explain changes observed in its functionality: The phosphomimetic mutation impairs cytochrome diffusion between respiratory complexes, enhances hemeprotein peroxidase and reactive oxygen species scavenging activities, and hinders caspase-dependent apoptosis. Our findings provide a framework to further investigate the modulation of mitochondrial activity by phosphorylated cytochrome and to develop novel therapeutic approaches based on its prosurvival effects.

PubMed: 28348229
DOI: 10.1073/pnas.1618008114

実験手法

SOLUTION NMR