Critical role of beta-hairpin formation in protein G folding

TitleCritical role of beta-hairpin formation in protein G folding
Publication TypeJournal Article
Year of Publication2000
AuthorsMcCallister, E. L., Alm E., & Baker D.
JournalNature structural biology
Volume7
Issue8
Pagination669-73
Date Published2000 Aug
ISSN1072-8368
KeywordsAmino Acid Substitution, Bacterial Proteins, Binding Sites, Immunoglobulin G, Kinetics, Models, Molecular, Mutation, Primary Publication, Protein Denaturation, Protein Folding, Protein Structure, Secondary, Protein Structure, Tertiary, Thermodynamics
Abstract

Comparison of the folding mechanisms of proteins with similar structures but very different sequences can provide fundamental insights into the determinants of protein folding mechanisms. Despite very little sequence similarity, the approximately 60 residue IgG binding domains of protein G and protein L both consist of a single helix packed against a four-stranded sheet formed by two symmetrically disposed beta-hairpins. We demonstrate that, as in the case of protein L, one of the two beta-turns of protein G is formed and the other disrupted in the folding transition state. Unlike protein L, however, in protein G it is the second beta-turn that is formed in the folding transition state ensemble. Substitution of an Asp residue by Ala in protein G that eliminates an i,i+2 side chain-main chain hydrogen bond in the second beta-turn slows the folding rate approximately 20-fold but has virtually no effect on the unfolding rate. Taken together with previous results, these findings suggest that the presence of an intact beta-turn in the folding transition state is a consequence of the overall topology of protein L and protein G, but the particular hairpin that is formed is determined by the detailed interatomic interactions that determine the free energies of formation of the isolated beta-hairpins.

Alternate JournalNat. Struct. Biol.
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