title: Preformed secondary structure drives the association reaction of GCN4-p1, a model coiled-coil system.
abstract: The structure of the transition state for the rate-limiting step in the folding and association of the homodimeric coiled-coil peptide GCN4-p1, was probed by mutational analysis. A series of quadruple amino acid replacements that spanned the helix propensity scale were made at the four external f positions in the heptad repeat. Equilibrium and kinetic circular dichroism studies demonstrate that both the stability and the unfolding and refolding rate constants vary with helix propensity but also reflect interactions of the altered side-chains with their local environments. Pairwise replacements and fragment studies show that the two C-terminal heptads are the likely source of the nucleating helices. Helix-helix recognition between preformed elements of secondary structure plays an important role in this fundamental folding reaction.
authors.affiliation: Department of Chemistry, Life Sciences Consortium, and Center for Biomolecular Structure and Function, The Pennsylvania State University, PA 16802, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Zitzewitz
authors.forename: B
authors.initials: B
authors.lastname: Ibarra-Molero
authors.forename: D R
authors.initials: DR
authors.lastname: Fishel
authors.forename: K L
authors.initials: KL
authors.lastname: Terry
authors.forename: C R
authors.initials: CR
authors.lastname: Matthews
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D004268:DNA-Binding Proteins; D019281:Dimerization; D005656:Fungal Proteins / Q000737:chemistry*; D007700:Kinetics; D016350:Leucine Zippers; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D011494:Protein Kinases / Q000737:chemistry*; D017433:Protein Structure, Secondary; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000737:chemistry*
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D011494:Protein Kinases