1o7k
From Proteopedia
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==Overview== | ==Overview== | ||
p47(phox) is a key cytosolic subunit required for activation of phagocyte, NADPH oxidase. The X-ray structure of the p47(phox) PX domain revealed two, distinct basic pockets on the membrane-binding surface, each occupied by a, sulfate. These two pockets have different specificities: one, preferentially binds phosphatidylinositol 3,4-bisphosphate, [PtdIns(3,4)P(2)] and is analogous to the phophatidylinositol 3-phosphate, (PtdIns3P)-binding pocket of p40(phox), while the other binds anionic, phospholipids such as phosphatidic acid (PtdOH) or phosphatidylserine. The, preference of this second site for PtdOH may be related to previously, observed activation of NADPH oxidase by PtdOH. Simultaneous occupancy of, the two phospholipid-binding pockets radically increases membrane, affinity. Strikingly, measurements for full-length p47(phox) show that, membrane interaction by the PX domain is masked by an intramolecular, association with the C-terminal SH3 domain (C-SH3). Either a site-specific, mutation in C-SH3 (W263R) or a mimic of the phosphorylated form of, p47(phox) [Ser(303, 304, 328, 359, 370)Glu] cause a transition from a, closed to an open conformation that binds membranes with a greater, affinity than the isolated PX domain. | p47(phox) is a key cytosolic subunit required for activation of phagocyte, NADPH oxidase. The X-ray structure of the p47(phox) PX domain revealed two, distinct basic pockets on the membrane-binding surface, each occupied by a, sulfate. These two pockets have different specificities: one, preferentially binds phosphatidylinositol 3,4-bisphosphate, [PtdIns(3,4)P(2)] and is analogous to the phophatidylinositol 3-phosphate, (PtdIns3P)-binding pocket of p40(phox), while the other binds anionic, phospholipids such as phosphatidic acid (PtdOH) or phosphatidylserine. The, preference of this second site for PtdOH may be related to previously, observed activation of NADPH oxidase by PtdOH. Simultaneous occupancy of, the two phospholipid-binding pockets radically increases membrane, affinity. Strikingly, measurements for full-length p47(phox) show that, membrane interaction by the PX domain is masked by an intramolecular, association with the C-terminal SH3 domain (C-SH3). Either a site-specific, mutation in C-SH3 (W263R) or a mimic of the phosphorylated form of, p47(phox) [Ser(303, 304, 328, 359, 370)Glu] cause a transition from a, closed to an open conformation that binds membranes with a greater, affinity than the isolated PX domain. | ||
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| + | ==Disease== | ||
| + | Known disease associated with this structure: Chronic granulomatous disease due to deficiency of NCF-1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608512 608512]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: sh3 domain]] | [[Category: sh3 domain]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:30:31 2007'' |
Revision as of 16:24, 12 November 2007
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HUMAN P47 PX DOMAIN COMPLEX WITH SULPHATES
Contents |
Overview
p47(phox) is a key cytosolic subunit required for activation of phagocyte, NADPH oxidase. The X-ray structure of the p47(phox) PX domain revealed two, distinct basic pockets on the membrane-binding surface, each occupied by a, sulfate. These two pockets have different specificities: one, preferentially binds phosphatidylinositol 3,4-bisphosphate, [PtdIns(3,4)P(2)] and is analogous to the phophatidylinositol 3-phosphate, (PtdIns3P)-binding pocket of p40(phox), while the other binds anionic, phospholipids such as phosphatidic acid (PtdOH) or phosphatidylserine. The, preference of this second site for PtdOH may be related to previously, observed activation of NADPH oxidase by PtdOH. Simultaneous occupancy of, the two phospholipid-binding pockets radically increases membrane, affinity. Strikingly, measurements for full-length p47(phox) show that, membrane interaction by the PX domain is masked by an intramolecular, association with the C-terminal SH3 domain (C-SH3). Either a site-specific, mutation in C-SH3 (W263R) or a mimic of the phosphorylated form of, p47(phox) [Ser(303, 304, 328, 359, 370)Glu] cause a transition from a, closed to an open conformation that binds membranes with a greater, affinity than the isolated PX domain.
Disease
Known disease associated with this structure: Chronic granulomatous disease due to deficiency of NCF-1 OMIM:[608512]
About this Structure
1O7K is a Single protein structure of sequence from Homo sapiens with SO4 as ligand. Structure known Active Site: API. Full crystallographic information is available from OCA.
Reference
Binding of the PX domain of p47(phox) to phosphatidylinositol 3,4-bisphosphate and phosphatidic acid is masked by an intramolecular interaction., Karathanassis D, Stahelin RV, Bravo J, Perisic O, Pacold CM, Cho W, Williams RL, EMBO J. 2002 Oct 1;21(19):5057-68. PMID:12356722
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