Prediction and structural characterization of an independently folding substructure in the src SH3 domain

TitlePrediction and structural characterization of an independently folding substructure in the src SH3 domain
Publication TypeJournal Article
Year of Publication1998
AuthorsYi, Q., Bystroff C., Rajagopal P., Klevit R. E., & Baker D.
JournalJournal of molecular biology
Volume283
Issue1
Pagination293-300
Date Published1998
ISSN0022-2836
KeywordsAmino Acid Sequence, Models, Molecular, Molecular Sequence Data, Nuclear Magnetic Resonance, Biomolecular, Oligopeptides, Primary Publication, Protein Conformation, Protein Folding, Protein Structure, Secondary, Proto-Oncogene Proteins pp60(c-src), src Homology Domains
Abstract

Previous studies of the conformations of peptides spanning the length of the alpha-spectrin SH3 domain suggested that SH3 domains lack independently folding substructures. Using a local structure prediction method based on the I-sites library of sequence-structure motifs, we identified a seven residue peptide in the src SH3 domain predicted to adopt a native-like structure, a type II beta-turn bridging unpaired beta-strands, that was not contained intact in any of the SH3 domain peptides studied earlier. NMR characterization confirmed that the isolated peptide, FKKGERL, adopts a structure similar to that adopted in the native protein: the NOE and 3JNHalpha coupling constant patterns were indicative of a type II beta-turn, and NOEs between the Phe and the Leu side-chains suggest that they are juxtaposed as in the prediction and the native structure. These results support the idea that high-confidence I-sites predictions identify protein segments that are likely to form native-like structures early in folding.

Alternate JournalJ. Mol. Biol.
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