Abstract
RECEPTOR protein-tyrosine kinases, through phosphorylation of specific tyrosine residues, generate high-affinity binding sites which direct assembly of multienzyme signalling complexes1,2. Many of these signalling proteins, including phospholipase Cγ, GTPase-activating protein and phosphatidylinositol-3-OH kinase, contain src-homology 2 (SH2) domains, which bind with high affinity and specificity to tyrosine-phosphorylated sequences3,4. The critical role played by SH2 domains in signalling has been highlighted by recent studies showing that mutation of specific phosphorylation sites on the platelet-derived growth factor receptor impair its association with phosphatidylinositol-3-OH kinase, preventing growth factor-induced mitogenesis5,6. Here we report the solution structure of an isolated SH2 domain from the 85K regulatory subunit of phosphatidylinositol-3-OH kinase, determined using multidimensional nuclear magnetic resonance spectroscopy. The structure is characterized by a central region of β-sheet flanked by two α-helices, with a highly flexible loop close to functionally important residues previously identified by site-directed mutagenesis7,8.
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Booker, G., Breeze, A., Downing, A. et al. Structure of an SH2 domain of the p85α subunit of phosphatidylinositol-3-OH kinase. Nature 358, 684–687 (1992). https://doi.org/10.1038/358684a0
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DOI: https://doi.org/10.1038/358684a0
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