2x11

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{{STRUCTURE_2x11| PDB=2x11 | SCENE= }}
 
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===CRYSTAL STRUCTURE OF THE COMPLETE EPHA2 ECTODOMAIN IN COMPLEX WITH EPHRIN A5 RECEPTOR BINDING DOMAIN===
 
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{{ABSTRACT_PUBMED_20228801}}
 
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==Function==
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==Crystal structure of the complete EphA2 ectodomain in complex with ephrin A5 receptor binding domain==
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[[http://www.uniprot.org/uniprot/EFNA5_HUMAN EFNA5_HUMAN]] Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Induces compartmentalized signaling within a caveolae-like membrane microdomain when bound to the extracellular domain of its cognate receptor. This signaling event requires the activity of the Fyn tyrosine kinase. Activates the EPHA3 receptor to regulate cell-cell adhesion and cytoskeletal organization. With the receptor EPHA2 may regulate lens fiber cells shape and interactions and be important for lens transparency maintenance. May function actively to stimulate axon fasciculation. The interaction of EFNA5 with EPHA5 also mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion. Cognate/functional ligand for EPHA7, their interaction regulates brain development modulating cell-cell adhesion and repulsion.<ref>PMID:10601038</ref><ref>PMID:11870224</ref>
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<StructureSection load='2x11' size='340' side='right'caption='[[2x11]], [[Resolution|resolution]] 4.83&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2x11]] is a 2 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=2X11 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X11 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]] 4.83&#8491;</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=2x11 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x11 OCA], [https://pdbe.org/2x11 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x11 RCSB], [https://www.ebi.ac.uk/pdbsum/2x11 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x11 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/EPHA2_HUMAN EPHA2_HUMAN] Genetic variations in EPHA2 are the cause of susceptibility to cataract cortical age-related type 2 (ARCC2) [MIM:[https://omim.org/entry/613020 613020]. A developmental punctate opacity common in the cortex and present in most lenses. The cataract is white or cerulean, increases in number with age, but rarely affects vision.<ref>PMID:19573808</ref> <ref>PMID:19649315</ref> Defects in EPHA2 are the cause of cataract posterior polar type 1 (CTPP1) [MIM:[https://omim.org/entry/116600 116600]. A subcapsular opacity, usually disk-shaped, located at the back of the lens. It can have a marked effect on visual acuity.<ref>PMID:19573808</ref> <ref>PMID:19005574</ref> <ref>PMID:19306328</ref> <ref>PMID:22570727</ref> Note=Overexpressed in several cancer types and promotes malignancy.<ref>PMID:19573808</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/EPHA2_HUMAN EPHA2_HUMAN] Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis.<ref>PMID:10655584</ref> <ref>PMID:16236711</ref> <ref>PMID:18339848</ref> <ref>PMID:19573808</ref> <ref>PMID:20679435</ref> <ref>PMID:20861311</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/x1/2x11_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=2x11 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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Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays.
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==About this Structure==
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An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly.,Seiradake E, Harlos K, Sutton G, Aricescu AR, Jones EY Nat Struct Mol Biol. 2010 Apr;17(4):398-402. Epub 2010 Mar 14. PMID:20228801<ref>PMID:20228801</ref>
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[[2x11]] is a 2 chain structure 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=2X11 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:020228801</ref><references group="xtra"/><references/>
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</div>
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<div class="pdbe-citations 2x11" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Ephrin|Ephrin]]
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*[[Ephrin receptor 3D structures|Ephrin receptor 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Receptor protein-tyrosine kinase]]
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[[Category: Large Structures]]
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[[Category: Aricescu, A R.]]
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[[Category: Aricescu AR]]
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[[Category: Harlos, K.]]
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[[Category: Harlos K]]
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[[Category: Jones, E Y.]]
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[[Category: Jones EY]]
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[[Category: Seiradake, E.]]
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[[Category: Seiradake E]]
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[[Category: Sutton, G.]]
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[[Category: Sutton G]]
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[[Category: Angiogenesis]]
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[[Category: Apoptosis]]
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[[Category: Cataract]]
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[[Category: Developmental protein]]
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[[Category: Erythropoietin-producing hepatocellular carcinoma]]
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[[Category: Kinase]]
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[[Category: Neurogenesis]]
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[[Category: Receptor]]
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[[Category: Receptor-signaling protein complex]]
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[[Category: Signaling platform]]
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[[Category: Signaling protein]]
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[[Category: Transferase]]
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Current revision

Crystal structure of the complete EphA2 ectodomain in complex with ephrin A5 receptor binding domain

PDB ID 2x11

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