title: Structural transformations of cytochrome c upon interaction with cardiolipin.
abstract: Interactions of cytochrome c (cyt c) with cardiolipin (CL) play a critical role in early stages of apoptosis. Upon binding to CL, cyt c undergoes changes in secondary and tertiary structure that lead to a dramatic increase in its peroxidase activity. Insertion of the protein into membranes, insertion of CL acyl chains into the protein interior, and extensive unfolding of cyt c after adsorption to the membrane have been proposed as possible modes for interaction of cyt c with CL. Dissociation of Met80 is accompanied by opening of the heme crevice and binding of another heme ligand. Fluorescence studies have revealed conformational heterogeneity of the lipid-bound protein ensemble with distinct polypeptide conformations that vary in the degree of protein unfolding. We correlate these recent findings to other biophysical observations and rationalize the role of experimental conditions in defining conformational properties and peroxidase activity of the cyt c ensemble. Latest time-resolved studies propose the trigger and the sequence of cardiolipin-induced structural transitions of cyt c.
authors.affiliation: Department of Chemistry, Dartmouth College, Hanover, NH 03755, United States.
authors.forename: Julia
authors.initials: J
authors.lastname: Muenzner
authors.affiliation: Department of Chemistry, Dartmouth College, Hanover, NH 03755, United States. Electronic address: ekaterina.pletneva@dartmouth.edu.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Pletneva
mesh_terms: D000818:Animals; D002308:Cardiolipins / Q000737:chemistry / Q000378:metabolism*; D002463:Cell Membrane Permeability; D045304:Cytochromes c / Q000737:chemistry* / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D006801:Humans; D011485:Protein Binding
chemical_list: D002308:Cardiolipins; D005609:Free Radicals; D006418:Heme; D045304:Cytochromes c
keywords: Apoptosis; Heme; Peroxidase; Protein folding