title: The crystal structure of the PX domain from p40(phox) bound to phosphatidylinositol 3-phosphate.
abstract: 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.
authors.affiliation: Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge CB2 2QH, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Bravo
authors.forename: D
authors.initials: D
authors.lastname: Karathanassis
authors.forename: C M
authors.initials: CM
authors.lastname: Pacold
authors.forename: M E
authors.initials: ME
authors.lastname: Pacold
authors.forename: C D
authors.initials: CD
authors.lastname: Ellson
authors.forename: K E
authors.initials: KE
authors.lastname: Anderson
authors.forename: P J
authors.initials: PJ
authors.lastname: Butler
authors.forename: I
authors.initials: I
authors.lastname: Lavenir
authors.forename: O
authors.initials: O
authors.lastname: Perisic
authors.forename: P T
authors.initials: PT
authors.lastname: Hawkins
authors.forename: L
authors.initials: L
authors.lastname: Stephens
authors.forename: R L
authors.initials: RL
authors.lastname: Williams
mesh_terms: 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
chemical_list: D018129:Phosphatidylinositol Phosphates; D010750:Phosphoproteins; D021122:Protein Subunits; C085072:neutrophil cytosol factor 40K; C055525:phosphatidylinositol 3-phosphate; D019255:NADPH Oxidases