8DVX

Structure of acetylated Pig somatic Cytochrome c (Aly39) at 1.5A

8DVX の概要

• エントリーDOI: 10.2210/pdb8dvx/pdb
• 分子名称: Cytochrome c, HEME C, HEXACYANOFERRATE(3-), ... (4 entities in total)
• 機能のキーワード: complex iv, complex iii, apoptosis, ischemia, skeletal muscle, acetylation, oxidoreductase, electron transport
• 由来する生物種: Sus scrofa (pig)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 50503.34

構造登録者

Edwards, B.F.P.,Huettemann, M.,Vaishnav, A.,Brunzelle, J.,Morse, P.,Wan, J. (登録日: 2022-07-30, 公開日: 2023-07-19, 最終更新日: 2024-10-09)

主引用文献

Morse, P.T.,Perez-Mejias, G.,Wan, J.,Turner, A.A.,Marquez, I.,Kalpage, H.A.,Vaishnav, A.,Zurek, M.P.,Huettemann, P.P.,Kim, K.,Arroum, T.,De la Rosa, M.A.,Chowdhury, D.D.,Lee, I.,Brunzelle, J.S.,Sanderson, T.H.,Malek, M.H.,Meierhofer, D.,Edwards, B.F.P.,Diaz-Moreno, I.,Huttemann, M.
Cytochrome c lysine acetylation regulates cellular respiration and cell death in ischemic skeletal muscle.
Nat Commun, 14:4166-4166, 2023

PubMed Abstract: Skeletal muscle is more resilient to ischemia-reperfusion injury than other organs. Tissue specific post-translational modifications of cytochrome c (Cytc) are involved in ischemia-reperfusion injury by regulating mitochondrial respiration and apoptosis. Here, we describe an acetylation site of Cytc, lysine 39 (K39), which was mapped in ischemic porcine skeletal muscle and removed by sirtuin5 in vitro. Using purified protein and cellular double knockout models, we show that K39 acetylation and acetylmimetic K39Q replacement increases cytochrome c oxidase (COX) activity and ROS scavenging while inhibiting apoptosis via decreased binding to Apaf-1, caspase cleavage and activity, and cardiolipin peroxidase activity. These results are discussed with X-ray crystallography structures of K39 acetylated (1.50 Å) and acetylmimetic K39Q Cytc (1.36 Å) and NMR dynamics. We propose that K39 acetylation is an adaptive response that controls electron transport chain flux, allowing skeletal muscle to meet heightened energy demand while simultaneously providing the tissue with robust resilience to ischemia-reperfusion injury.

PubMed: 37443314
DOI: 10.1038/s41467-023-39820-8

実験手法

X-RAY DIFFRACTION (1.5 Å)