8AJ8

Structure of p110 gamma bound to the p84 regulatory subunit

8AJ8 の概要

• エントリーDOI: 10.2210/pdb8aj8/pdb
• 分子名称: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, Phosphoinositide 3-kinase regulatory subunit 6 (2 entities in total)
• 機能のキーワード: pi3k, pik3cg, pik3r6, phosphoinositide 3-kinase, p110, p84, signaling protein
• 由来する生物種: Sus scrofa (pig); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 846402.87

構造登録者

Burke, J.E.,Williams, R.L.,Zhang, X. (登録日: 2022-07-27, 公開日: 2023-03-22, 最終更新日: 2024-02-07)

主引用文献

Rathinaswamy, M.K.,Jenkins, M.L.,Duewell, B.R.,Zhang, X.,Harris, N.J.,Evans, J.T.,Stariha, J.T.B.,Dalwadi, U.,Fleming, K.D.,Ranga-Prasad, H.,Yip, C.K.,Williams, R.L.,Hansen, S.D.,Burke, J.E.
Molecular basis for differential activation of p101 and p84 complexes of PI3K gamma by Ras and GPCRs.
Cell Rep, 42:112172-112172, 2023

PubMed Abstract: Class IB phosphoinositide 3-kinase (PI3Kγ) is activated in immune cells and can form two distinct complexes (p110γ-p84 and p110γ-p101), which are differentially activated by G protein-coupled receptors (GPCRs) and Ras. Using a combination of X-ray crystallography, hydrogen deuterium exchange mass spectrometry (HDX-MS), electron microscopy, molecular modeling, single-molecule imaging, and activity assays, we identify molecular differences between p110γ-p84 and p110γ-p101 that explain their differential membrane recruitment and activation by Ras and GPCRs. The p110γ-p84 complex is dynamic compared with p110γ-p101. While p110γ-p101 is robustly recruited by Gβγ subunits, p110γ-p84 is weakly recruited to membranes by Gβγ subunits alone and requires recruitment by Ras to allow for Gβγ activation. We mapped two distinct Gβγ interfaces on p101 and the p110γ helical domain, with differences in the C-terminal domain of p84 and p101 conferring sensitivity of p110γ-p101 to Gβγ activation. Overall, our work provides key insight into the molecular basis for how PI3Kγ complexes are activated.

PubMed: 36842083
DOI: 10.1016/j.celrep.2023.112172

実験手法

X-RAY DIFFRACTION (8.5 Å)