title: A breakdown of symmetry in the folding transition state of protein L.
abstract: The 62 residue IgG binding domain of protein L consists of a central alpha-helix packed on a four-stranded beta-sheet formed by N and C-terminal beta-hairpins. The overall topology of the protein is quite symmetric: the beta-hairpins have similar lengths and make very similar interactions with the central helix. Characterization of the effects of 70 point mutations distributed throughout the protein on the kinetics of folding and unfolding reveals that this symmetry is completely broken during folding; the first beta-hairpin is largely structured while the second beta-hairpin and helix are largely disrupted in the folding transition state ensemble. The results are not consistent with a "hydrophobic core first" picture of protein folding; the first beta-hairpin appears to be at least as ordered at the rate limiting step in folding as the hydrophobic core.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Kim
authors.forename: C
authors.initials: C
authors.lastname: Fisher
authors.forename: D
authors.initials: D
authors.lastname: Baker
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002942:Circular Dichroism; D005453:Fluorescence; D019791:Guanidine / Q000494:pharmacology; D006860:Hydrogen Bonding; D007074:Immunoglobulin G / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D010462:Peptostreptococcus / Q000737:chemistry*; D017354:Point Mutation / Q000235:genetics; D011489:Protein Denaturation / Q000187:drug effects; D017510:Protein Folding; D020673:Protein Renaturation; D017433:Protein Structure, Secondary / Q000187:drug effects; D017434:Protein Structure, Tertiary / Q000187:drug effects; D012997:Solvents; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; C055047:Ig L-binding protein, Peptostreptococcus; D007074:Immunoglobulin G; D012997:Solvents; D019791:Guanidine