High-resolution single-molecule characterization of the enzymatic states in Escherichia coli F1-ATPase

Philos Trans R Soc Lond B Biol Sci. 2012 Dec 24;368(1611):20120023. doi: 10.1098/rstb.2012.0023. Print 2013 Feb 5.

Abstract

The rotary motor F(1)-ATPase from the thermophilic Bacillus PS3 (TF(1)) is one of the best-studied of all molecular machines. F(1)-ATPase is the part of the enzyme F(1)F(O)-ATP synthase that is responsible for generating most of the ATP in living cells. Single-molecule experiments have provided a detailed understanding of how ATP hydrolysis and synthesis are coupled to internal rotation within the motor. In this work, we present evidence that mesophilic F(1)-ATPase from Escherichia coli (EF(1)) is governed by the same mechanism as TF(1) under laboratory conditions. Using optical microscopy to measure rotation of a variety of marker particles attached to the γ-subunit of single surface-bound EF(1) molecules, we characterized the ATP-binding, catalytic and inhibited states of EF(1). We also show that the ATP-binding and catalytic states are separated by 35±3°. At room temperature, chemical processes occur faster in EF(1) than in TF(1), and we present a methodology to compensate for artefacts that occur when the enzymatic rates are comparable to the experimental temporal resolution. Furthermore, we show that the molecule-to-molecule variation observed at high ATP concentration in our single-molecule assays can be accounted for by variation in the orientation of the rotating markers.

Publication types

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

MeSH terms

  • Actin Cytoskeleton / chemistry
  • Adenosine Diphosphate / chemistry
  • Adenosine Triphosphate / biosynthesis
  • Adenosine Triphosphate / chemistry
  • Bacterial Proton-Translocating ATPases / chemistry*
  • Binding Sites
  • Enzyme Activation
  • Enzyme Assays
  • Escherichia coli / enzymology*
  • Escherichia coli Proteins / chemistry*
  • Hydrodynamics
  • Hydrolysis
  • Magnesium / chemistry
  • Optical Imaging / methods
  • Protein Binding
  • Protein Conformation
  • Temperature
  • Time Factors

Substances

  • Escherichia coli Proteins
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Bacterial Proton-Translocating ATPases
  • Magnesium