title: Single-molecule fluorescence experiments determine protein folding transition path times.
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.
authors.affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892-0520, USA. chunghoi@niddk.nih.gov
authors.forename: Hoi Sung
authors.initials: HS
authors.lastname: Chung
authors.forename: Kevin
authors.initials: K
authors.lastname: McHale
authors.forename: John M
authors.initials: JM
authors.lastname: Louis
authors.forename: William A
authors.initials: WA
authors.lastname: Eaton
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry*; D050556:Fatty Acid-Binding Proteins; D031541:Fluorescence Resonance Energy Transfer; D007700:Kinetics; D016013:Likelihood Functions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017785:Photons; D011487:Protein Conformation; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; C106410:Fnbp1 protein, mouse; C034284:IgG Fc-binding protein, Streptococcus