Important role of hydrogen bonds in the structurally polarized transition state for folding of the src SH3 domain

TitleImportant role of hydrogen bonds in the structurally polarized transition state for folding of the src SH3 domain
Publication TypeJournal Article
Year of Publication1998
AuthorsGrantcharova, V. P., Riddle D. S., Santiago J. V., & Baker D.
JournalNature structural biology
Volume5
Issue8
Pagination714-20
Date Published1998 Aug
ISSN1072-8368
KeywordsFlow Injection Analysis, Guanidine, Hydrogen Bonding, Models, Molecular, Mutagenesis, Site-Directed, Mutation, Primary Publication, Protein Denaturation, Protein Folding, Protein Structure, Secondary, Proto-Oncogene Proteins pp60(c-src), src Homology Domains
Abstract

Experimental and theoretical studies on the folding of small proteins such as the chymotrypsin inhibitor 2 (CI-2) and the P22 Arc repressor suggest that the folding transition state is an expanded version of the native state with most interactions partially formed. Here we report that this picture does not hold generally: a hydrogen bond network involving two beta-turns and an adjacent hydrophobic cluster appear to be formed in the folding transition state of the src SH3 domain, while the remainder of the polypeptide chain is largely unstructured. Comparison with data on other small proteins suggests that this structural polarization is a consequence of the topology of the SH3 domain fold. The non-uniform distribution of structure in the folding transition state provides a challenging test for computational models of the folding process.

Alternate JournalNat. Struct. Biol.
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