1HE8

Ras G12V - PI 3-kinase gamma complex

1HE8 の概要

• エントリーDOI: 10.2210/pdb1he8/pdb
• 関連するPDBエントリー: 1E8Y 1E8Z
• 分子名称: PHOSPHATIDYLINOSITOL 3-KINASE CATALYTIC SUBUNIT, GAMMA ISOFORM, TRANSFORMING PROTEIN P21/H-RAS-1, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: kinase/hydrolase, complex (phosphoinositide kinase-ras), phosphoinositide 3-kinase gamma - h-ras g12v complex, phosphatidylinositol 3-kinase, pi3k, pi 3-k, pi 3-kinase, second messenger generation, ras effector, h-ras g12v, oncogene protein, gmppnp, gtp, ras-binding domain, heat domain, kinase-hydrolase complex
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 130090.72

構造登録者

Pacold, M.E.,Suire, S.,Perisic, O.,Lara-Gonzalez, S.,Davis, C.T.,Hawkins, P.T.,Walker, E.H.,Stephens, L.,Eccleston, J.F.,Williams, R.L. (登録日: 2000-11-20, 公開日: 2001-01-08, 最終更新日: 2023-12-13)

主引用文献

Pacold, M.E.,Suire, S.,Perisic, O.,Lara-Gonzalez, S.,Davis, C.T.,Walker, E.H.,Hawkins, P.T.,Stephens, L.,Eccleston, J.F.,Williams, R.L.
Crystal Structure and Functional Analysis of Ras Binding to its Effector Phosphoinositide 3-Kinase Gamma
Cell(Cambridge,Mass.), 103:931-, 2000

PubMed Abstract: Ras activation of phosphoinositide 3-kinase (PI3K) is important for survival of transformed cells. We find that PI3Kgamma is strongly and directly activated by H-Ras G12V in vivo or by GTPgammaS-loaded H-Ras in vitro. We have determined a crystal structure of a PI3Kgamma/Ras.GMPPNP complex. A critical loop in the Ras binding domain positions Ras so that it uses its switch I and switch II regions to bind PI3Kgamma. Mutagenesis shows that interactions with both regions are essential for binding PI3Kgamma. Ras also forms a direct contact with the PI3Kgamma catalytic domain. These unique Ras/PI3Kgamma interactions are likely to be shared by PI3Kalpha. The complex with Ras shows a change in the PI3K conformation that may represent an allosteric component of Ras activation.

PubMed: 11136978
DOI: 10.1016/S0092-8674(00)00196-3

実験手法

X-RAY DIFFRACTION (3 Å)