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{{STRUCTURE_1he8| PDB=1he8 | SCENE= }}
==RAS G12V - PI 3-KINASE GAMMA COMPLEX==
===RAS G12V - PI 3-KINASE GAMMA COMPLEX===
<StructureSection load='1he8' size='340' side='right' caption='[[1he8]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
{{ABSTRACT_PUBMED_11136978}}
== Structural highlights ==
<table><tr><td colspan='2'>[[1he8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The April 2012 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ras Protein'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2012_4 10.2210/rcsb_pdb/mom_2012_4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HE8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HE8 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1e8y|1e8y]], [[1e8z|1e8z]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol_3-kinase Phosphatidylinositol 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.137 2.7.1.137] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1he8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1he8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1he8 RCSB], [http://www.ebi.ac.uk/pdbsum/1he8 PDBsum]</span></td></tr>
</table>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/he/1he8_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


==Function==
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<ref>PMID:11136978</ref>
[[http://www.uniprot.org/uniprot/PK3CG_HUMAN PK3CG_HUMAN]] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to ADRBK1 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.<ref>PMID:7624799</ref><ref>PMID:12163475</ref><ref>PMID:15294162</ref><ref>PMID:16094730</ref><ref>PMID:21393242</ref>  


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[1he8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The April 2012 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ras Protein''  by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2012_4 10.2210/rcsb_pdb/mom_2012_4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HE8 OCA].
</div>


==See Also==
==See Also==
*[[Phosphoinositide 3-Kinases|Phosphoinositide 3-Kinases]]
*[[Phosphoinositide 3-Kinases|Phosphoinositide 3-Kinases]]
*[[Phsphatidylinositol 3-kinase|Phsphatidylinositol 3-kinase]]
== References ==
 
<references/>
==Reference==
__TOC__
<ref group="xtra">PMID:011136978</ref><references group="xtra"/><references/>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Phosphatidylinositol 3-kinase]]
[[Category: Phosphatidylinositol 3-kinase]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Ras Protein]]
[[Category: Ras Protein]]
[[Category: Davis, C T.]]
[[Category: Davis, C T]]
[[Category: Eccleston, J F.]]
[[Category: Eccleston, J F]]
[[Category: Hawkins, P T.]]
[[Category: Hawkins, P T]]
[[Category: Lara-Gonzalez, S.]]
[[Category: Lara-Gonzalez, S]]
[[Category: Pacold, M E.]]
[[Category: Pacold, M E]]
[[Category: Perisic, O.]]
[[Category: Perisic, O]]
[[Category: Stephens, L.]]
[[Category: Stephens, L]]
[[Category: Suire, S.]]
[[Category: Suire, S]]
[[Category: Walker, E H.]]
[[Category: Walker, E H]]
[[Category: Williams, R L.]]
[[Category: Williams, R L]]
[[Category: Gmppnp]]
[[Category: Gmppnp]]
[[Category: Gtp]]
[[Category: Gtp]]
Line 36: Line 54:
[[Category: Kinase/hydrolase]]
[[Category: Kinase/hydrolase]]
[[Category: Oncogene protein]]
[[Category: Oncogene protein]]
[[Category: Phosphatidylinositol 3-kinase]]
[[Category: Phosphoinositide 3-kinase gamma - h-ras g12v complex]]
[[Category: Phosphoinositide 3-kinase gamma - h-ras g12v complex]]
[[Category: Pi 3-k]]
[[Category: Pi 3-k]]

Revision as of 21:05, 22 December 2014

RAS G12V - PI 3-KINASE GAMMA COMPLEX

1he8, resolution 3.00Å

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