6MRP

Structure of the Bovine p85a BH domain R228E mutant

6MRP の概要

• エントリーDOI: 10.2210/pdb6mrp/pdb
• 分子名称: Phosphatidylinositol 3-kinase regulatory subunit alpha (2 entities in total)
• 機能のキーワード: gap protein, signalling protein, signaling protein
• 由来する生物種: Bos taurus (Bovine)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48951.98

構造登録者

Moore, S.A.,Marshall, J.D.,Anderson, D.H. (登録日: 2018-10-15, 公開日: 2019-01-30, 最終更新日: 2024-10-23)

主引用文献

Marshall, J.D.S.,Mellor, P.,Ruan, X.,Whitecross, D.E.,Moore, S.A.,Anderson, D.H.
Insight into the PTEN - p85 alpha interaction and lipid binding properties of the p85 alpha BH domain.
Oncotarget, 9:36975-36992, 2018

PubMed Abstract: The phosphatidylinositol 3-kinase (PI3K) pathway plays a key role in regulating cell growth and cell survival and is frequently deregulated in cancer cells. p85α regulates the p110α lipid kinase, and also stabilizes and stimulates PTEN, the lipid phosphatase that downregulates this pathway. In this report, we determined that the p85α BH domain binds several phosphorylated phosphoinositide lipids, an interaction that could help localize p85α to membranes rich in these lipids. We also identified key residues responsible for mediating PTEN - p85α complex formation. Based on these experimental results, a docking model for the PTEN - p85α BH domain complex was developed that is consistent with the known binding interactions for both PTEN and p85α. This model involves extensive side-chain and peptide backbone contacts between both the PASE and C2 domains of PTEN with the p85α BH domains. The p85α BH domain residues shown to be important for PTEN binding were p85α residues E212, Q221, K225, R228 and H234. We also verified experimentally the importance of PTEN-E91 in mediating the interaction with the p85α BH domain. These results shed new light on the mechanism of PTEN regulation by p85α.

PubMed: 30651929
DOI: 10.18632/oncotarget.26432

実験手法

X-RAY DIFFRACTION (2.403 Å)