Probing a Complex of Cytochrome c and Cardiolipin by Magnetic Circular Dichroism Spectroscopy: Implications for the Initial Events in Apoptosis

被引：77

作者：

Bradley, Justin M. ^{[1
,2
]}

Silkstone, Gary ^{[3
]}

Wilson, Michael T. ^{[3
]}

Cheesman, Myles R. ^{[1
,2
]}

Butt, Julea N. ^{[1
,2
]}

机构：

[1] Univ E Anglia, Sch Chem, Ctr Mol & Struct Biochem, Norwich NR4 7TJ, Norfolk, England

[2] Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England

[3] Univ Essex, Dept Biol Sci, Colchester CO4 3SQ, Essex, England

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2011年 / 133卷 / 49期

基金：

英国生物技术与生命科学研究理事会;

关键词：

PROTEIN ENVIRONMENT; PEROXIDASE-ACTIVITY; NITRITE REDUCTASE; CARBON-MONOXIDE; HEME IRON; IN-SITU; LIGAND; REDOX; MITOCHONDRIA; HEMOPROTEINS;

D O I：

10.1021/ja209144h

中图分类号：

O6 [化学];

学科分类号：

070301 [无机化学];

摘要：

Oxidation of cardiolipin (CL) by its complex with cytochrome c (cyt c) plays a crucial role in triggering apoptosis. Through a combination of magnetic circular dichroism spectroscopy and potentiometric titrations, we show that both the ferric and ferrous forms of the heme group of a CL:cyt c complex exist as multiple conformers at a physiologically relevant pH of 7.4. For the ferric state, these conformers are His/Lys- and His/OH--ligated. The ferrous state is predominantly high-spin and, most likely, His/-. Interconversion of the ferric and ferrous conformers is described by a single midpoint potential of -80 +/- 9 mV vs SHE. These results suggest that CL oxidation in mitochondria could occur by the reaction of molecular oxygen with the ferrous CL:cyt c complex in addition to the well-described reaction of peroxides with the ferric form.

引用

页码：19676 / 19679

页数：4

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