2iwl

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[[Image:2iwl.png|left|200px]]
 
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{{STRUCTURE_2iwl| PDB=2iwl | SCENE= }}
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==Structure of the PX Domain of Phosphoinositide 3-Kinase-C2alpha==
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<StructureSection load='2iwl' size='340' side='right'caption='[[2iwl]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2iwl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IWL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IWL FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2iwl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iwl OCA], [https://pdbe.org/2iwl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2iwl RCSB], [https://www.ebi.ac.uk/pdbsum/2iwl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2iwl ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/P3C2A_HUMAN P3C2A_HUMAN] Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin-mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin-independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain (MLC) phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function.<ref>PMID:9337861</ref> <ref>PMID:10766823</ref> <ref>PMID:10805725</ref> <ref>PMID:11239472</ref> <ref>PMID:12719431</ref> <ref>PMID:16215232</ref> <ref>PMID:21081650</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/iw/2iwl_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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/main_output.php?pdb_ID=2iwl ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Phox homology (PX) domains, which have been identified in a variety of proteins involved in cell signaling and membrane trafficking, have been shown to interact with phosphoinositides (PIs) with different affinities and specificities. To elucidate the structural origin of diverse PI specificities of PX domains, we determined the crystal structure of the PX domain from phosphoinositide 3-kinase C2alpha (PI3K-C2alpha), which binds phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)). To delineate the mechanism by which this PX domain interacts with membranes, we measured the membrane binding of the wild type domain and mutants by surface plasmon resonance and monolayer techniques. This PX domain contains a signature PI-binding site that is optimized for PtdIns(4,5)P(2) binding. The membrane binding of the PX domain is initiated by nonspecific electrostatic interactions followed by the membrane penetration of hydrophobic residues. Membrane penetration is specifically enhanced by PtdIns(4,5)P(2). Furthermore, the PX domain displayed significantly higher PtdIns(4,5)P(2) membrane affinity and specificity when compared with the PI3K-C2alpha C2 domain, demonstrating that high affinity PtdIns(4,5)P(2) binding was facilitated by the PX domain in full-length PI3K-C2alpha. Together, these studies provide new structural insight into the diverse PI specificities of PX domains and elucidate the mechanism by which the PI3K-C2alpha PX domain interacts with PtdIns(4,5)P(2)-containing membranes and thereby mediates the membrane recruitment of PI3K-C2alpha.
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===STRUCTURE OF THE PX DOMAIN OF PHOSPHOINOSITIDE 3-KINASE-C2ALPHA===
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Structural and membrane binding analysis of the Phox homology domain of phosphoinositide 3-kinase-C2alpha.,Stahelin RV, Karathanassis D, Bruzik KS, Waterfield MD, Bravo J, Williams RL, Cho W J Biol Chem. 2006 Dec 22;281(51):39396-406. Epub 2006 Oct 12. PMID:17038310<ref>PMID:17038310</ref>
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{{ABSTRACT_PUBMED_17038310}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 2iwl" style="background-color:#fffaf0;"></div>
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[[2iwl]] is a 1 chain structure of [[Phosphoinositide 3-Kinases]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IWL OCA].
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==See Also==
==See Also==
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*[[Phosphoinositide 3-Kinases|Phosphoinositide 3-Kinases]]
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*[[Phosphoinositide 3-kinase 3D structures|Phosphoinositide 3-kinase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:017038310</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Bravo, J.]]
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[[Category: Large Structures]]
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[[Category: Karathanassis, D.]]
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[[Category: Bravo J]]
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[[Category: Williams, R L.]]
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[[Category: Karathanassis D]]
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[[Category: Kinase]]
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[[Category: Williams RL]]
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[[Category: Nuclear protein]]
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[[Category: Phosphoinositide]]
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[[Category: Phosphoinositide 3-kinase]]
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[[Category: Phosphorylation]]
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[[Category: Pi3k]]
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[[Category: Px domain]]
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[[Category: Transferase]]
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Current revision

Structure of the PX Domain of Phosphoinositide 3-Kinase-C2alpha

PDB ID 2iwl

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