title: The role of helix formation in the folding of a fully alpha-helical coiled coil.
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).
authors.affiliation: The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia 19104-6059, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Sosnick
authors.forename: S
authors.initials: S
authors.lastname: Jackson
authors.forename: R R
authors.initials: RR
authors.lastname: Wilk
authors.forename: S W
authors.initials: SW
authors.lastname: Englander
authors.forename: W F
authors.initials: WF
authors.lastname: DeGrado
mesh_terms: D000595:Amino Acid Sequence; D007700:Kinetics; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D013816:Thermodynamics