title: Electrostatically driven second-sphere ligand switch between high and low reorganization energy forms of native cytochrome c.
abstract: We have employed a combination of protein film voltammetry, time-resolved vibrational spectroelectrochemistry and molecular dynamics simulations to evaluate the electron-transfer reorganization free energy (λ) of cytochrome c (Cyt) in electrostatic complexes that mimic some basic features of protein-protein and protein-lipid interactions. The results reveal the existence of two native-like conformations of Cyt that present significantly different λ values. Conversion from the high to the low λ forms is triggered by electrostatic interactions, and involves the rupture of a weak H-bond between first- (M80) and second-sphere (Y67) ligands of the heme iron, as a distinctive feature of the conformational switch. The two flexible Ω loops operate as transducers of the electrostatic signal. This fine-tuning effect is abolished in the Y67F Cyt mutant, which presents a λ value similar to the WT protein in electrostatic complexes. We propose that interactions of Cyt with the natural redox partner proteins activate a similar mechanism to minimize the reorganization energy of interprotein electron transfer.
authors: Departamento de Química Inorgánica, Analítica y Química Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pab. 2, piso 1, C1428EHA-Buenos Aires, Argentina.
authors: Damián
authors: D
authors: Alvarez-Paggi
authors: María A
authors: MA
authors: Castro
authors: Verónica
authors: V
authors: Tórtora
authors: Laura
authors: L
authors: Castro
authors: Rafael
authors: R
authors: Radi
authors: Daniel H
authors: DH
authors: Murgida
mesh_terms: D000818:Animals; D045304:Cytochromes c / Q000737:chemistry* / Q000235:genetics; D055664:Electrochemical Techniques; D004579:Electron Transport; D006736:Horses; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D017354:Point Mutation; D013059:Spectrum Analysis, Raman; D055672:Static Electricity; D014443:Tyrosine / Q000737:chemistry / Q000235:genetics
chemical_list: D014443:Tyrosine; D045304:Cytochromes c