The crystal structure of the PX domain from p40(phox) bound to phosphatidylinositol 3-phosphate.
More than 50 human proteins with a wide range of functions have a 120 residue phosphoinositide binding module known as the PX domain. The 1.7 A X-ray crystal structure of the PX domain from the p40(phox) subunit of NADPH oxidase bound to PtdIns(3)P shows that the PX domain embraces the 3-phosphate on one side of a water-filled, positively charged pocket and reveals how 3-phosphoinositide specificity is achieved. A chronic granulomatous disease (CGD)-associated mutation in the p47(phox) PX domain that abrogates PtdIns(3)P binding maps to a conserved Arg that does not directly interact with the phosphoinositide but instead appears to stabilize a critical lipid binding loop. The SH3 domain present in the full-length protein does not affect soluble PtdIns(3)P binding to the p40(phox) PX domain.
Bravo
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Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge CB2 2QH, United Kingdom.
Karathanassis
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Pacold
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Pacold
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Ellson
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Anderson
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Butler
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PJ
Lavenir
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Perisic
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Hawkins
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Stephens
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Williams
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D000595:Amino Acid Sequence; D001665:Binding Sites; D002151:Calorimetry; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019255:NADPH Oxidases / Q000737:chemistry; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D016415:Sequence Alignment; D014461:Ultracentrifugation
D018129:Phosphatidylinositol Phosphates; D010750:Phosphoproteins; D021122:Protein Subunits; C085072:neutrophil cytosol factor 40K; C055525:phosphatidylinositol 3-phosphate; D019255:NADPH Oxidases