Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains
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Journal ArticlePublication Date
2000-09-13Keywords
1-Phosphatidylinositol 3-Kinase; Amino Acid Sequence; Amino Acid Substitution; Binding Sites; Conserved Sequence; Crystallography, X-Ray; Inositol Phosphates; Models, Molecular; Molecular Sequence Data; Mutagenesis, Site-Directed; Phosphatidylinositols; Protein Conformation; Protein Structure, Secondary; Receptors, Cytoplasmic and Nuclear; Recombinant Proteins; Sequence Alignment; Sequence Homology, Amino Acid; src Homology DomainsLife Sciences
Medicine and Health Sciences
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Lipid second messengers generated by phosphoinositide (PI) 3-kinases regulate diverse cellular functions through interaction with pleckstrin homology (PH) domains in modular signaling proteins. The PH domain of Grp1, a PI 3-kinase-activated exchange factor for Arf GTPases, selectively binds phosphatidylinositol 3,4,5-trisphosphate with high affinity. We have determined the structure of the Grp1 PH domain in the unliganded form and bound to inositol 1,3,4,5-tetraphosphate. A novel mode of phosphoinositide recognition involving a 20-residue insertion within the beta6/beta7 loop explains the unusually high specificity of the Grp1 PH domain and the promiscuous 3-phosphoinositide binding typical of several PH domains including that of protein kinase B. When compared to other PH domains, general determinants of 3-phosphoinositide recognition and specificity can be deduced.Source
Mol Cell. 2000 Aug;6(2):385-94.
DOI
10.1016/S1097-2765(00)00038-1Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34048PubMed ID
10983985Related Resources
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