title: Pathway of protein folding.
abstract: The order of formation of substructures in the folding of barnase has been determined by a protein engineering procedure and corroborated and complemented by NMR experiments. Early events are the formation of the centre of the beta-sheet and the C-terminus of the major alpha-helix. These later dock to form the major hydrophobic core. Structural studies of fragments of barnase in solution show that a peptide that spans the major alpha-helix is found to contain a significant fraction of its C-terminal region in the helical structures. The formation of the native secondary structure as an early event in folding and in isolated fragments is accompanied by considerable burial of hydrophobic surfaces. The experimental data support a model for protein folding in which initiation sites in secondary structure are driven by local hydrophobic interactions, and their docking via further hydrophobic interactions drives the formation of tertiary structure.
authors.affiliation: Cambridge Centre for Protein Engineering, University Chemical Laboratory, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Fersht
authors.forename: A
authors.initials: A
authors.lastname: Matouschek
authors.forename: J
authors.initials: J
authors.lastname: Sancho
authors.forename: L
authors.initials: L
authors.lastname: Serrano
authors.forename: S
authors.initials: S
authors.lastname: Vuilleumier
mesh_terms: D001426:Bacterial Proteins; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012260:Ribonucleases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D010446:Peptide Fragments; D012260:Ribonucleases; C019760:Bacillus amyloliquefaciens ribonuclease