title: Becoming a peroxidase: cardiolipin-induced unfolding of cytochrome c.
abstract: Interactions of cytochrome c (cyt c) with a unique mitochondrial glycerophospholipid cardiolipin (CL) are relevant for the protein's function in oxidative phosphorylation and apoptosis. Binding to CL-containing membranes promotes cyt c unfolding and dramatically enhances the protein's peroxidase activity, which is critical in early stages of apoptosis. We have employed a collection of seven dansyl variants of horse heart cyt c to probe the sequence of steps in this functional transformation. Kinetic measurements have unraveled four distinct processes during CL-induced cyt c unfolding: rapid protein binding to CL liposomes; rearrangements of protein substructures with small unfolding energies; partial insertion of the protein into the lipid bilayer; and extensive protein restructuring leading to "open" extended structures. While early rearrangements depend on a hierarchy of foldons in the native structure, the later process of large-scale unfolding is influenced by protein interactions with the membrane surface. The opening of the cyt c structure exposes the heme group, which enhances the protein's peroxidase activity and also frees the C-terminal helix to aid in the translocation of the protein through CL membranes.
authors.affiliation: Department of Chemistry, Dartmouth College , Hanover, New Hampshire 03755, United States.
authors.forename: Julia
authors.initials: J
authors.lastname: Muenzner
authors.forename: Jason R
authors.initials: JR
authors.lastname: Toffey
authors.forename: Yuning
authors.initials: Y
authors.lastname: Hong
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Pletneva
mesh_terms: D000818:Animals; D002308:Cardiolipins / Q000737:chemistry* / Q000378:metabolism; D045304:Cytochromes c / Q000737:chemistry / Q000378:metabolism*; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D006736:Horses; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009195:Peroxidase / Q000737:chemistry / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000737:chemistry; D011485:Protein Binding; D011489:Protein Denaturation
chemical_list: C496906:1-myristoyl-2-(12-((5-dimethylamino-1-naphthalenesulfonyl)amino)dodecanoyl)-sn-glycero-3-phosphocholine; D002308:Cardiolipins; D008081:Liposomes; D010713:Phosphatidylcholines; D006418:Heme; D045304:Cytochromes c; D009195:Peroxidase