Prediction and structural characterization of an independently folding substructure in the src SH3 domain.
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.
Yi
Q
Q
Department of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
Bystroff
C
C
Rajagopal
P
P
Klevit
R E
RE
Baker
D
D
D000595:Amino Acid Sequence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry*; D018909:src Homology Domains
D009842:Oligopeptides; D016392:Proto-Oncogene Proteins pp60(c-src)