3ZCF

Structure of recombinant human cytochrome c

3ZCF の概要

• エントリーDOI: 10.2210/pdb3zcf/pdb
• 分子名称: CYTOCHROME C, HEME C (3 entities in total)
• 機能のキーワード: electron transport, respiration, apoptosis, electron transfer
• 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: 4
• 化学式量合計: 49036.34

構造登録者

Rajagopal, B.S.,Worrall, J.A.R.,Hough, M.A. (登録日: 2012-11-20, 公開日: 2013-10-23, 最終更新日: 2024-10-23)

主引用文献

Rajagopal, B.S.,Edzuma, A.N.,Hough, M.A.,Blundell, K.L.I.M.,Kagan, V.E.,Kapralov, A.A.,Fraser, L.A.,Butt, J.N.,Silkstone, G.G.,Wilson, M.T.,Svistunenko, D.A.,Worrall, J.A.R.
The Hydrogen Peroxide Induced Radical Behaviour in Human Cytochrome C Phospholipid Complexes: Implications for the Enhanced Pro-Apoptotic Activity of the G41S Mutant
Biochem.J., 456:441-, 2013

PubMed Abstract: We have investigated whether the pro-apoptotic properties of the G41S mutant of human cytochrome c can be explained by a higher than wild-type peroxidase activity triggered by phospholipid binding. A key complex in mitochondrial apoptosis involves cytochrome c and the phospholipid cardiolipin. In this complex cytochrome c has its native axial Met(80) ligand dissociated from the haem-iron, considerably augmenting the peroxidase capability of the haem group upon H2O2 binding. By EPR spectroscopy we reveal that the magnitude of changes in the paramagnetic haem states, as well as the yield of protein-bound free radical, is dependent on the phospholipid used and is considerably greater in the G41S mutant. A high-resolution X-ray crystal structure of human cytochrome c was determined and, in combination with the radical EPR signal analysis, two tyrosine residues, Tyr(46) and Tyr(48), have been rationalized to be putative radical sites. Subsequent single and double tyrosine-to-phenylalanine mutations revealed that the EPR signal of the radical, found to be similar in all variants, including G41S and wild-type, originates not from a single tyrosine residue, but is instead a superimposition of multiple EPR signals from different radical sites. We propose a mechanism of multiple radical formations in the cytochrome c-phospholipid complexes under H2O2 treatment, consistent with the stabilization of the radical in the G41S mutant, which elicits a greater peroxidase activity from cytochrome c and thus has implications in mitochondrial apoptosis.

PubMed: 24099549
DOI: 10.1042/BJ20130758

実験手法

X-RAY DIFFRACTION (1.65 Å)