title: The effects of ATP and sodium chloride on the cytochrome c-cardiolipin interaction: the contrasting behavior of the horse heart and yeast proteins.
abstract: In cells a portion of cytochrome c (cyt c) (15-20%) is tightly bound to cardiolipin (CL), one of the phospholipids constituting the mitochondrial membrane. The CL-bound protein, which has nonnative tertiary structure, altered heme pocket, and disrupted Fe(III)-M80 axial bond, is thought to play a role in the apoptotic process. This has attracted considerable interest in order to clarify the mechanisms governing the cyt c-CL interaction. Herein we have investigated the binding reaction of CL with the c-type cytochromes from horse heart and yeast. Although the two proteins possess a similar tertiary architecture, yeast cyt c displays lower stability and, contrary to the equine protein, it does not bind ATP and lacks pro-apoptotic activity. The study has been performed in the absence and in the presence of ATP and NaCl, two compounds that influence the (horse cyt c)-CL binding process and, thus, the pro-apoptotic activity of the protein. The two proteins behave differently: while CL interaction with horse cyt c is strongly influenced by the two effectors, no effect is observed for yeast cyt c. It is noteworthy that NaCl induces dissociation of the (horse cyt c)-CL complex but has no influence on that of yeast cyt c. The differences found for the two proteins highlight that specific structural factors, such as the different local structure conformation of the regions involved in the interactions with either CL or ATP, can significantly affect the behavior of cyt c in its reaction with liposomes and the subsequent pro-apoptotic action of the protein.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Rome 'Tor Vergata', Via Montpellier 1, I-00133 Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Sinibaldi
authors.forename: Enrica
authors.initials: E
authors.lastname: Droghetti
authors.forename: Fabio
authors.initials: F
authors.lastname: Polticelli
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Piro
authors.forename: Donato
authors.initials: D
authors.lastname: Di Pierro
authors.forename: Tommaso
authors.initials: T
authors.lastname: Ferri
authors.forename: Giulietta
authors.initials: G
authors.lastname: Smulevich
authors.forename: Roberto
authors.initials: R
authors.lastname: Santucci
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D002308:Cardiolipins / Q000737:chemistry*; D002417:Cattle; D045304:Cytochromes c / Q000737:chemistry*; D006418:Heme / Q000737:chemistry; D006736:Horses; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry; D009994:Osmolar Concentration; D011485:Protein Binding; D055503:Protein Multimerization; D055550:Protein Stability; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D012965:Sodium Chloride / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013059:Spectrum Analysis, Raman; D017186:Titrimetry
chemical_list: C014059:CYC1 protein, S cerevisiae; D002308:Cardiolipins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D006418:Heme; D012965:Sodium Chloride; D000255:Adenosine Triphosphate; D045304:Cytochromes c