Loop formation in unfolded polypeptide chains on the picoseconds to microseconds time scale

Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2163-8. doi: 10.1073/pnas.0611087104. Epub 2007 Feb 6.

Abstract

Intrachain loop formation allows unfolded polypeptide chains to search for favorable interactions during protein folding. We applied triplet-triplet energy transfer between a xanthone moiety and naphthylalanine to directly measure loop formation in various unfolded polypeptide chains with loop regions consisting of polyserine, poly(glycine-serine) or polyproline. By combination of femtosecond and nanosecond laserflash experiments loop formation could be studied over many orders of magnitude in time from picoseconds to microseconds. The results reveal processes on different time scales indicating motions on different hierarchical levels of the free energy surface. A minor (<15%) very fast reaction with a time constant of approximately 3 ps indicates equilibrium conformations with donor and acceptor in contact at the time of the laserflash. Complex kinetics of loop formation were observed on the 50- to 500-ps time scale, which indicate motions within a local well on the energy landscape. Conformations within this well can form loops by undergoing local motions without having to cross major barriers. Exponential kinetics observed on the 10- to 100-ns time scale are caused by diffusional processes involving large-scale motions that allow the polypeptide chain to explore the complete conformational space. These results indicate that the free energy landscape for unfolded polypeptide chains and native proteins have similar properties. The presence of local energy minima reduces the conformational space and accelerates the conformational search for energetically favorable local intrachain contacts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / analogs & derivatives
  • Alanine / chemistry
  • Diffusion
  • Energy Transfer*
  • Kinetics
  • Models, Molecular*
  • Motion
  • Peptides / chemistry*
  • Protein Folding*
  • Protein Structure, Secondary
  • Time Factors
  • Xanthones / chemistry

Substances

  • Peptides
  • Xanthones
  • 1-naphthylalanine
  • xanthone
  • Alanine