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Title
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Structural basis for IL-4 receptor phosphopeptide recognition by the IRS-1 PTB domain.
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Authors
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M.M.Zhou,
B.Huang,
E.T.Olejniczak,
R.P.Meadows,
S.B.Shuker,
M.Miyazaki,
T.Trüb,
S.E.Shoelson,
S.W.Fesik.
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Ref.
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Nat Struct Biol, 1996,
3,
388-393.
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PubMed id
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Abstract
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We present the NMR structure of the PTB domain of insulin receptor substrate-1
(IRS-1) complexed to a tyrosine-phosphorylated peptide derived from the IL-4
receptor. Despite the lack of sequence homology and different binding
specificity, the overall fold of the protein is similar to that of the Shc PTB
domain and closely resembles that of PH domains. However, the PTB domain of
IRS-1 is smaller than that of Shc (110 versus 170 residues) and binds to
phosphopeptides in a distinct manner. We explain the phosphopeptide binding
specificity based on the structure of the complex and results of site-directed
mutagenesis experiments.
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