Coupling H+ transport and ATP synthesis in F1F0-ATP synthases: glimpses of interacting parts in a dynamic molecular machine

J Exp Biol. 1997 Jan;200(Pt 2):217-24. doi: 10.1242/jeb.200.2.217.

Abstract

Reversible, F1F0-type ATPases (also termed F-ATP synthases) catalyze the synthesis of ATP during oxidative phosphorylation. In animal cells, the enzyme traverses the inner mitochondrial membrane and uses the energy of an H+ electrochemical gradient, generated by electron transport, in coupling H+ translocation to ATP formation. Closely related enzymes are found in the plasma membrane of bacteria such as Escherichia coli, where the enzymes function reversibly depending upon nutritional circumstance. The F1F0-type enzymes are more distantly related to a second family of H(+)-translocating ATPases, the vacuolar-type or V-ATPases. Recent structural information has provided important hints as to how these enzymes couple H+ transport to the chemical work of ATP synthesis. The simplest F1F0-type enzymes, e.g. as in E. coli, are composed of eight types of subunits in an unusual stoichiometry of alpha 3 beta 3 gamma delta epsilon (F1) and a1b2c12 (F0). F1 extends from the membrane, with the alpha and beta subunits alternating around a central subunit gamma. ATP synthesis occurs alternately in different beta subunits, the cooperative tight binding of ADP + Pi at one catalytic site being coupled to ATP release at a second. The differences in binding affinities appear to be caused by rotation of the gamma subunit in the center of the alpha 3 beta 3 hexamer. The gamma subunit traverses a 4.5 nm stalk connecting the catalytic subunits to the membrane-traversing F0 sector. Subunit c is the H(+)-translocating subunit of F0. Protonation/deprotonation of Asp61 in the center of the membrane is coupled to structural changes in an extramembranous loop of subunit c which interacts with both the gamma and epsilon subunits. Subunits gamma and epsilon appear to move from one subunit c to another as ATP is synthesized. The torque of such movement is proposed to cause the rotation of gamma within the alpha 3 beta 3 complex. Four protons are translocated for each ATP synthesized. The movement of gamma and epsilon therefore probably involves a unit of four c subunits. The organization of subunits in F0 remains a mystery; it will have to be understood if we are to understand the mechanism of torque generation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adenosine Triphosphatases
  • Adenosine Triphosphate / biosynthesis*
  • Animals
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Catalysis
  • Cattle
  • Energy Metabolism
  • Escherichia coli / enzymology
  • Gram-Negative Anaerobic Bacteria / enzymology
  • Mitochondria, Heart / enzymology
  • Models, Molecular
  • Protein Binding
  • Protein Conformation*
  • Proton Pumps / metabolism*
  • Proton-Motive Force*
  • Proton-Translocating ATPases / chemistry*
  • Proton-Translocating ATPases / metabolism
  • Rotation
  • Structure-Activity Relationship
  • Torque

Substances

  • Bacterial Proteins
  • Proton Pumps
  • Adenosine Triphosphate
  • Adenosine Triphosphatases
  • Proton-Translocating ATPases