Contrasting roles for symmetrically disposed beta-turns in the folding of a small protein

J Mol Biol. 1997 Dec 12;274(4):588-96. doi: 10.1006/jmbi.1997.1374.

Abstract

To investigate the role of turns in protein folding, we have characterized the effects of combinatorial and site-directed mutations in the two beta-turns of peptostreptococcal protein L on folding thermodynamics and kinetics. Sequences of folded variants recovered from combinatorial libraries using a phase display selection method were considerably more variable in the second turn than in the first turn. These combinatorial mutants as well as strategically placed point mutants in the two turns had a similar range of thermodynamic stabilities, but strikingly different folding kinetics. A glycine to alanine substitution in the second beta-turn increased the rate of unfolding more than tenfold but had little effect on the rate of folding, while mutation of a symmetrically disposed glycine residue in the first turn had little effect on unfolding but slowed the rate of folding nearly tenfold. These results demonstrate that the role of beta-turns in protein folding is strongly context-dependent, and suggests that the first turn is formed and the second turn disrupted in the folding transition state.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics*
  • Bacteriophages / genetics
  • Base Sequence
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis
  • Mutation
  • Point Mutation
  • Protein Folding*

Substances

  • Bacterial Proteins
  • Ig L-binding protein, Peptostreptococcus