title: Interactions involved in grasping and locking of the inhibitory peptide IF1 by mitochondrial ATP synthase.
abstract: When mitochondria become deenergized, futile ATP hydrolysis is prevented by reversible binding of an endogenous inhibitory peptide called IF1 to ATP synthase. Between initial IF1 binding and IF1 locking the enzyme experiences large conformational changes. While structural studies give access to analysis of the dead-end inhibited state, transient states have thus far not been described. Here, we studied both initial and final states by reporting, for the first time, the consequences of mutations of Saccharomyces cerevisiae ATP synthase on its inhibition by IF1. Kinetic studies allowed the identification of amino acids or motifs of the enzyme that are involved in recognition and/or locking of IF1 α-helical midpart. This led to an outline of IF1 binding process. In the recognition step, protruding parts of α and especially β subunits grasp IF1, most likely by a few residues of its α-helical midpart. Locking IF1 within the αβ interface involves additional residues of both subunits. Interactions of the α and β subunits with the foot of the γ subunit might contribute to locking and stabilizing of the dead-end state.
authors: UMR 8221, CNRS-CEA-Université Paris-Sud, iBiTec-S, CEA Saclay, 91191 Gif-sur-Yvette, France. Electronic address: qian.wu@cea.fr.
authors: Qian
authors: Q
authors: Wu
authors: UMR 8221, CNRS-CEA-Université Paris-Sud, iBiTec-S, CEA Saclay, 91191 Gif-sur-Yvette, France. Electronic address: tiona.andrianaivomananjaona@cea.fr.
authors: Tiona
authors: T
authors: Andrianaivomananjaona
authors: Institut de Biochimie et Génétique Cellulaires, UMR 5095 CNRS, Université Victor Segalen, 1, rue Camille Saint Saëns, 33077 Bordeaux, France. Electronic address: tetaud@ibgc.cnrs.fr.
authors: Emmanuel
authors: E
authors: Tetaud
authors: UMR 8221, CNRS-CEA-Université Paris-Sud, iBiTec-S, CEA Saclay, 91191 Gif-sur-Yvette, France. Electronic address: vcorvest@calixar.com.
authors: Vincent
authors: V
authors: Corvest
authors: UMR 8221, CNRS-CEA-Université Paris-Sud, iBiTec-S, CEA Saclay, 91191 Gif-sur-Yvette, France. Electronic address: francis.haraux@cea.fr.
authors: Francis
authors: F
authors: Haraux
mesh_terms: D007700:Kinetics; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010455:Peptides / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism
chemical_list: D010455:Peptides; D025261:Mitochondrial Proton-Translocating ATPases
keywords: ATP synthase; IF1 inhibitory peptide; Kinetics; Mitochondrion; Protein–protein interaction; Regulation