1he8 | pdb_00001he8
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. 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 Page seeded by OCA on Fri May 2 18:45:27 2008
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Homo sapiens
- Phosphatidylinositol 3-kinase
- Protein complex
- Davis, C T.
- Eccleston, J F.
- Hawkins, P T.
- Lara-Gonzalez, S.
- Pacold, M E.
- Perisic, O.
- Stephens, L.
- Suire, S.
- Walker, E H.
- Williams, R L.
- Gmppnp
- Gtp
- H-ras g12v
- Heat domain
- Oncogene protein
- Phosphoinositide 3-kinase gamma - h-ras g12v complex
- Pi 3-k
- Pi 3-kinase
- Pi3k
- Ras effector
- Ras-binding domain
- Second messenger generation
