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

✍ Scribed by Sosnick, Tobin R.; Jackson, Sharon; Wilk, Rosemarie R.; Englander, S. Walter; DeGrado, William F.

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 652 KB
• Volume: 24
• Category: Article
• ISSN: 0887-3585
• DOI: 10.1002/(sici)1097-0134(199604)24:4<427::aid-prot2>3.0.co;2-b

✦ Synopsis

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).