Protein folding transition states probed by loop extension

Protein Sci. 2008 Jan;17(1):183-6. doi: 10.1110/ps.073217708.

Abstract

We propose a new way to characterize protein folding transition states by (1) insertion of one or more residues into an unstructured protein loop, (2) measurement of the effect on protein folding kinetics and thermodynamics, and (3) analysis of the results in terms of a rate-equilibrium free energy relationship, alpha(Loop). alpha(Loop) reports on the fraction of molecules that form the perturbed loop in the transition state. Interpretation of the changes in equilibrium free energy using standard polymer theory can help detect residual structure in the unfolded state. We illustrate our approach with data for the model proteins CI2 and the alpha spectrin SH3 domain.

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Kinetics
  • Protein Folding*
  • Proteins / chemistry*
  • Proteins / metabolism*
  • Thermodynamics

Substances

  • Bacterial Proteins
  • Proteins