Understanding ATP synthesis: structure and mechanism of the F1-ATPase (Review).
To couple the energy present in the electrochemical proton gradient, established across the mitochondrial membrane by the respiratory chain, to the formation of ATP from ADP and Pi, ATP-synthase goes through a sequence of coordinated conformational changes of its major subunits (alpha, beta). These changes are induced by the rotation of the gamma subunit driven by the translocation of protons through the c subunit of the membrane portion of the enzyme. During this process, the F1-portion of the ATP-synthase adopts at least two major conformations depending on the occupancy of the beta subunits: one with two nucleotides, the other with three. In the two-nucleotide structure, the empty beta subunit adopts an open conformation that is highly different from the other conformations of beta subunits: tight, loose and closed. The three-dimensional structures of the F1-ATPase in each of these two major conformations provide a framework for understanding the mechanism of energy coupling by the enzyme. The energetics associated with two different models of the reaction steps, analysed using molecular dynamics calculations, show that three-nucleotide intermediates do not occur in configurations with an open beta subunit; instead, they are stabilized by completing a jaw-like motion that closes the beta subunit around the nucleotide. Consequently, the energy driven, major conformational change takes place with the beta subunits in the tight, loose and closed conformation.
Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
J Alfonso
JA
Leyva
Mario A
MA
Bianchet
L Mario
LM
Amzel
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000737:chemistry* / Q000378:metabolism*
D021122:Protein Subunits; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases