1HE8

Ras G12V - PI 3-kinase gamma complex

Summary for 1HE8

• Entry DOI: 10.2210/pdb1he8/pdb
• Related: 1E8Y 1E8Z
• Descriptor: PHOSPHATIDYLINOSITOL 3-KINASE CATALYTIC SUBUNIT, GAMMA ISOFORM, TRANSFORMING PROTEIN P21/H-RAS-1, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: 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
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 2
• Total formula weight: 130090.72

Authors

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. (deposition date: 2000-11-20, release date: 2001-01-08, Last modification date: 2023-12-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3 Å)