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Extended cardiolipin anchorage to cytochrome c: a model for protein–mitochondrial membrane binding

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Abstract

Two models have been proposed to explain the interaction of cytochrome c with cardiolipin (CL) vesicles. In one case, an acyl chain of the phospholipid accommodates into a hydrophobic channel of the protein located close the Asn52 residue, whereas the alternative model considers the insertion of the acyl chain in the region of the Met80-containing loop. In an attempt to clarify which proposal offers a more appropriate explanation of cytochrome c–CL binding, we have undertaken a spectroscopic and kinetic study of the wild type and the Asn52Ile mutant of iso-1-cytochrome c from yeast to investigate the interaction of cytochrome c with CL vesicles, considered here a model for the CL-containing mitochondrial membrane. Replacement of Asn52, an invariant residue located in a small helix segment of the protein, may provide data useful to gain novel information on which region of cytochrome c is involved in the binding reaction with CL vesicles. In agreement with our recent results revealing that two distinct transitions take place in the cytochrome c–CL binding reaction, data obtained here support a model in which two (instead of one, as considered so far) adjacent acyl chains of the liposome are inserted, one at each of the hydrophobic sites, into the same cytochrome c molecule to form the cytochrome c–CL complex.

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Acknowledgments

This research was funded in part by grants from the Italian MIUR (PRIN 2007KAWXCL to R.S. and FIRB RBNE03PX83 to M.C.) and local Italian Grant (ex 60%) to G.S.

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Correspondence to Roberto Santucci.

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Sinibaldi, F., Howes, B.D., Piro, M.C. et al. Extended cardiolipin anchorage to cytochrome c: a model for protein–mitochondrial membrane binding. J Biol Inorg Chem 15, 689–700 (2010). https://doi.org/10.1007/s00775-010-0636-z

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  • DOI: https://doi.org/10.1007/s00775-010-0636-z

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