How subunit coupling produces the gamma-subunit rotary motion in F1-ATPase

Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1192-7. doi: 10.1073/pnas.0708746105. Epub 2008 Jan 23.

Abstract

F(o)F(1)-ATP synthase manufactures the energy "currency," ATP, of living cells. The soluble F(1) portion, called F(1)-ATPase, can act as a rotary motor, with ATP binding, hydrolysis, and product release, inducing a torque on the gamma-subunit. A coarse-grained plastic network model is used to show at a residue level of detail how the conformational changes of the catalytic beta-subunits act on the gamma-subunit through repulsive van der Waals interactions to generate a torque that drives unidirectional rotation, as observed experimentally. The simulations suggest that the calculated 85 degrees substep rotation is driven primarily by ATP binding and that the subsequent 35 degrees substep rotation is produced by product release from one beta-subunit and a concomitant binding pocket expansion of another beta-subunit. The results of the simulation agree with single-molecule experiments [see, for example, Adachi K, et al. (2007) Cell 130:309-321] and support a tri-site rotary mechanism for F(1)-ATPase under physiological condition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Catalysis
  • Cattle
  • Computational Biology / methods
  • Hydrolysis
  • Mitochondrial Proteins / chemistry*
  • Mitochondrial Proteins / metabolism
  • Models, Chemical
  • Molecular Motor Proteins / chemistry*
  • Molecular Motor Proteins / metabolism
  • Protein Conformation
  • Protein Subunits / chemistry*
  • Protein Subunits / metabolism
  • Proton-Translocating ATPases / chemistry*
  • Proton-Translocating ATPases / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Thermodynamics
  • Torque

Substances

  • Mitochondrial Proteins
  • Molecular Motor Proteins
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • Proton-Translocating ATPases