1o7k
From Proteopedia
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==Overview== | ==Overview== | ||
| - | p47(phox) is a key cytosolic subunit required for activation of phagocyte | + | 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== | ==Disease== | ||
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[[Category: Bravo, J.]] | [[Category: Bravo, J.]] | ||
[[Category: Karathanassis, D.]] | [[Category: Karathanassis, D.]] | ||
| - | [[Category: Pacold, C | + | [[Category: Pacold, C M.]] |
[[Category: Perisic, O.]] | [[Category: Perisic, O.]] | ||
| - | [[Category: Williams, R | + | [[Category: Williams, R L.]] |
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: nadph oxidase]] | [[Category: nadph oxidase]] | ||
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[[Category: sh3 domain]] | [[Category: sh3 domain]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:14:18 2008'' |
Revision as of 12:14, 21 February 2008
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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 as ligand. Known structural/functional Site: . 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
Page seeded by OCA on Thu Feb 21 14:14:18 2008
