title: How general is the nucleation-condensation mechanism?
abstract: We investigate the structures of the major folding transition states of nine proteins by correlation of published Phi-values with inter-residue contact maps. Combined with previous studies on six proteins, the analysis suggests that at least 10 of the 15 small globular proteins fold via a nucleation-condensation mechanism with a concurrent build-up of secondary and tertiary structure contacts, but a structural consolidation that is clearly nonuniformly distributed over the molecule and most intense in a single structural region suggesting the occurrence of a single folding nucleus. However, on average helix- and sheet-forming residues show somewhat larger Phi-values in the major transition state, suggesting that secondary structure formation is one important driving force in the nucleation-condensation in many proteins and that secondary-structure forming residues tend to be more prominent in folding nuclei. We synthesize the combined information on these 10 of 15 proteins into a unified nucleation-condensation mechanism which also accounts for effects described by the framework, hydrophobic collapse, zipper, and funnel models.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158-2517, USA.
authors.forename: Bengt
authors.initials: B
authors.lastname: Nölting
authors.forename: David A
authors.initials: DA
authors.lastname: Agard
mesh_terms: D008956:Models, Chemical; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; D011506:Proteins