The role of helix formation in the folding of a fully alpha-helical coiled coil

Proteins. 1996 Apr;24(4):427-32. doi: 10.1002/(SICI)1097-0134(199604)24:4<427::AID-PROT2>3.0.CO;2-B.

Abstract

To determine when secondary structure forms as two chains coalesce to form an alpha-helical dimer, the folding rates of variants of the coiled coil region of GCN4 were compared. Residues at non-perturbing positions along the exterior length of the helices were substituted one at a time with alanine and glycine to vary helix propensity and therefore dimer stability. For all variants, the bimolecular folding rate remains largely unchanged; the unfolding rate changes to largely account for the change in stability. Thus, contrary to most folding models, widespread helix is not yet formed at the rate-limiting step in the folding pathway. The high-energy transition state is a collapsed form that contains little if any secondary structure, as suggested for the globular protein cytochrome c (Sosnick et al., Proteins 24: 413-426, 1996).

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Kinetics
  • Molecular Sequence Data
  • Protein Conformation*
  • Protein Folding*
  • Thermodynamics