The role of helix formation in the folding of a fully alpha-helical coiled coil.
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).
Sosnick
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The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia 19104-6059, USA.
Jackson
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Wilk
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Englander
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DeGrado
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D000595:Amino Acid Sequence; D007700:Kinetics; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D013816:Thermodynamics