1O7K

human p47 PX domain complex with sulphates

1O7K の概要

• エントリーDOI: 10.2210/pdb1o7k/pdb
• 関連するPDBエントリー: 1GD5 1K4U
• 分子名称: NEUTROPHIL CYTOSOL FACTOR 1, SULFATE ION (3 entities in total)
• 機能のキーワード: p47, nadph oxidase, px domain, phospholipid-binding, phosphoinositide-binding, sh3 domain
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm, cytosol : P14598
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 48311.26

構造登録者

Karathanassis, D.,Bravo, J.,Perisic, O.,Pacold, C.M.,Williams, R.L. (登録日: 2002-11-07, 公開日: 2002-11-20, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2 Å)