Single-molecule fluorescence experiments determine protein folding transition path times

Science. 2012 Feb 24;335(6071):981-4. doi: 10.1126/science.1215768.

Abstract

The transition path is the tiny fraction of an equilibrium molecular trajectory when a transition occurs as the free-energy barrier between two states is crossed. It is a single-molecule property that contains all the mechanistic information on how a process occurs. As a step toward observing transition paths in protein folding, we determined the average transition-path time for a fast- and a slow-folding protein from a photon-by-photon analysis of fluorescence trajectories in single-molecule Förster resonance energy transfer experiments. Whereas the folding rate coefficients differ by a factor of 10,000, the transition-path times differ by a factor of less than 5, which shows that a fast- and a slow-folding protein take almost the same time to fold when folding actually happens. A very simple model based on energy landscape theory can explain this result.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Carrier Proteins / chemistry*
  • Fatty Acid-Binding Proteins
  • Fluorescence Resonance Energy Transfer
  • Kinetics
  • Likelihood Functions
  • Models, Molecular
  • Molecular Sequence Data
  • Photons
  • Protein Conformation
  • Protein Folding*
  • Protein Interaction Domains and Motifs
  • Protein Structure, Tertiary
  • Thermodynamics

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Fatty Acid-Binding Proteins
  • Fnbp1 protein, mouse
  • IgG Fc-binding protein, Streptococcus