1O7K

human p47 PX domain complex with sulphates

Summary for 1O7K

• Entry DOI: 10.2210/pdb1o7k/pdb
• Related: 1GD5 1K4U
• Descriptor: NEUTROPHIL CYTOSOL FACTOR 1, SULFATE ION (3 entities in total)
• Functional Keywords: p47, nadph oxidase, px domain, phospholipid-binding, phosphoinositide-binding, sh3 domain
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm, cytosol : P14598
• Total number of polymer chains: 3
• Total formula weight: 48311.26

Authors

Karathanassis, D.,Bravo, J.,Perisic, O.,Pacold, C.M.,Williams, R.L. (deposition date: 2002-11-07, release date: 2002-11-20, Last modification date: 2024-11-06)

Primary citation

Karathanassis, D.,Stahelin, R.V.,Bravo, J.,Perisic, O.,Pacold, C.M.,Cho, W.,Williams, R.L.
Binding of the Px Domain of P47Phox to Phosphatidylinositol 3.4-Bisphosphate and Phosphatidic Acid is Masked by an Intramolecular Interaction
Embo J., 21:5057-, 2002

PubMed Abstract: 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.

PubMed: 12356722
DOI: 10.1093/EMBOJ/CDF519

Experimental method

X-RAY DIFFRACTION (2 Å)