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PDBsum entry 2pna
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Signalling protein
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PDB id
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2pna
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References listed in PDB file
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Key reference
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Title
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Structure of an sh2 domain of the p85 alpha subunit of phosphatidylinositol-3-Oh kinase.
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Authors
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G.W.Booker,
A.L.Breeze,
A.K.Downing,
G.Panayotou,
I.Gout,
M.D.Waterfield,
I.D.Campbell.
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Ref.
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Nature, 1992,
358,
684-687.
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PubMed id
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Abstract
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Receptor protein-tyrosine kinases, through phosphorylation of specific tyrosine
residues, generate high-affinity binding sites which direct assembly of
multienzyme signalling complexes. Many of these signalling proteins, including
phospholipase C gamma, GTPase-activating protein and phosphatidylinositol-3-OH
kinase, contain src-homology 2 (SH2) domains, which bind with high affinity and
specificity to tyrosine-phosphorylated sequences. 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 mitogenesis. 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 beta-sheet flanked by two alpha-helices, with a highly flexible loop
close to functionally important residues previously identified by site-directed
mutagenesis.
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