title: Intermediates and the folding of proteins L and G.
abstract: We use a minimalist protein model, in combination with a sequence design strategy, to determine differences in primary structure for proteins L and G, which are responsible for the two proteins folding through distinctly different folding mechanisms. We find that the folding of proteins L and G are consistent with a nucleation-condensation mechanism, each of which is described as helix-assisted beta-1 and beta-2 hairpin formation, respectively. We determine that the model for protein G exhibits an early intermediate that precedes the rate-limiting barrier of folding, and which draws together misaligned secondary structure elements that are stabilized by hydrophobic core contacts involving the third beta-strand, and presages the later transition state in which the correct strand alignment of these same secondary structure elements is restored. Finally, the validity of the targeted intermediate ensemble for protein G was analyzed by fitting the kinetic data to a two-step first-order reversible reaction, proving that protein G folding involves an on-pathway early intermediate, and should be populated and therefore observable by experiment.
authors.affiliation: Department of Bioengineering, 472 Donner Laboratory, University of California, Berkeley, Berkeley, CA 94720-1762, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Brown
authors.forename: Teresa
authors.initials: T
authors.lastname: Head-Gordon
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D019295:Computational Biology; D006801:Humans; D007700:Kinetics; D008962:Models, Theoretical; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D001426:Bacterial Proteins