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An investigation into a cardiolipin acyl chain insertion site in cytochrome c

Rajagopal, Badri S and Silkstone, Gary G and Nicholls, Peter and Wilson, Michael T and Worrall, Jonathan AR (2012) 'An investigation into a cardiolipin acyl chain insertion site in cytochrome c.' Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1817 (5). pp. 780-791. ISSN 0005-2728

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Mitochondrial cytochrome c associates with the phosphoplipid cardiolipin (CL) through a combination of electrostatic and hydrophobic interactions. The latter occurs by insertion into cytochrome c of an acyl chain, resulting in the dissociation of the axial Met-80 heme-iron ligand. The resulting five coordinate cytochrome c/CL complex has peroxidatic properties leading to peroxidation of CL and dissociation of the complex. These events are considered to be pre-apoptotic and culminate with release of cytochrome c from the mitochondria into the cytoplasm. Two distinct surface regions on cytochrome c have been suggested to mediate CL acyl chain insertion and this study has probed one of these regions. We have constructed a series of alanine mutants aimed at disrupting a surface cleft formed between residues 67-71 and 82-85. The physicochemical properties, peroxidase activity, CL binding, and kinetics of carbon monoxide (CO) binding to the ferrous cytochrome c/CL complex have been assessed for the individual mutants. Our findings reveal that the majority of mutants are capable of binding CL in the same apparent stoichiometry as the wild-type protein, with the extent to which the Met-80 ligand is bound in the ferrous cytochrome c/CL complex being mutant specific at neutral pH. Mutation of the species conserved Arg-91 residue, that anchors the cleft, results in the greatest changes to physicochemical properties of the protein leading to a change in the CL binding ratio required to effect structural changes and to the ligand-exchange properties of the ferrous cytochrome c/CL complex. © 2012 Elsevier B.V. © 2012 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: Cytochrome c; Phospholipids; Cardiolipin; Apoptosis; Peroxidase; Ligand binding
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 13 Mar 2013 22:24
Last Modified: 18 Aug 2022 11:15

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