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spinqualitylabelsall models 1he8, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

RAS G12V-PI 3-KINASE GAMMA COMPLEX

Overview

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.

About this Structure

1HE8 is a [Protein complex] structure of sequences from [Homo sapiens] with MG and GNP as [ligands]. Active as [[1]], with EC number [2.7.1.137]. Full crystallographic information is available from [OCA].

Reference

Crystal structure and functional analysis of Ras binding to its effector phosphoinositide 3-kinase gamma., Pacold ME, Suire S, Perisic O, Lara-Gonzalez S, Davis CT, Walker EH, Hawkins PT, Stephens L, Eccleston JF, Williams RL, Cell. 2000 Dec 8;103(6):931-43. PMID:11136978

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