Binding of a high affinity phosphotyrosyl peptide to the Src SH2 domain: crystal structures of the complexed and peptide-free forms.
The crystal structure of the Src SH2 domain complexed with a high affinity 11-residue phosphopeptide has been determined at 2.7 A resolution by X-ray diffraction. The peptide binds in an extended conformation and makes primary interactions with the SH2 domain at six central residues: PQ(pY)EEI. The phosphotyrosine and the isoleucine are tightly bound by two well-defined pockets on the protein surface, resulting in a complex that resembles a two-pronged plug engaging a two-holed socket. The glutamate residues are in solvent-exposed environments in the vicinity of basic side chains of the SH2 domain, and the two N-terminal residues cap the phosphotyrosine-binding site. The crystal structure of Src SH2 in the absence of peptide has been determined at 2.5 A resolution, and comparison with the structure of the high affinity complex reveals only localized and relatively small changes.
Waksman
G
G
Rockefeller University, New York, New York 10021.
Shoelson
S E
SE
Pant
N
N
Cowburn
D
D
Kuriyan
J
J
D000595:Amino Acid Sequence; D001665:Binding Sites; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010748:Phosphopeptides / Q000378:metabolism*; D011487:Protein Conformation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D016415:Sequence Alignment; D014443:Tyrosine / Q000378:metabolism; D014961:X-Ray Diffraction
D005971:Glutamates; D010748:Phosphopeptides; D018698:Glutamic Acid; D014443:Tyrosine; D016392:Proto-Oncogene Proteins pp60(c-src)