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Title
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Binding of a high affinity phosphotyrosyl peptide to the Src SH2 domain: crystal structures of the complexed and peptide-free forms.
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Authors
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G.Waksman,
S.E.Shoelson,
N.Pant,
D.Cowburn,
J.Kuriyan.
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Ref.
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Cell, 1993,
72,
779-790.
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PubMed id
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Abstract
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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.
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