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

• Published in: Journal of molecular biology 1998, Vol.283 (1), p.293-300
• Main Authors: Yi, Qian, Bystroff, Chris, Rajagopal, Ponni, Klevit, Rachel E, Baker, David
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; folding initiation site; local structure; Models, Molecular; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular; Oligopeptides - chemical synthesis; Oligopeptides - chemistry; Protein Conformation; Protein Folding; Protein Structure, Secondary; Proto-Oncogene Proteins pp60(c-src) - chemistry; SH3 domain; src Homology Domains; β-turn
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1006/jmbi.1998.2072

Previous studies of the conformations of peptides spanning the length of the α-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 β-turn bridging unpaired β-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 3 J NH α coupling constant patterns were indicative of a type II β-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.