3gxu: Difference between revisions

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-[[Image:3gxu.png|left|200px]]
-<!--
+==Crystal structure of Eph receptor and ephrin complex==
-The line below this paragraph, containing "STRUCTURE_3gxu", creates the "Structure Box" on the page.
+<StructureSection load='3gxu' size='340' side='right'caption='[[3gxu]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3gxu]] 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=3GXU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GXU FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
--->
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3gxu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gxu OCA], [https://pdbe.org/3gxu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gxu RCSB], [https://www.ebi.ac.uk/pdbsum/3gxu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gxu ProSAT]</span></td></tr>
-{{STRUCTURE_3gxu|  PDB=3gxu  |  SCENE=  }}
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/EPHA4_HUMAN EPHA4_HUMAN] Receptor tyrosine kinase which binds membrane-bound ephrin 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. Highly promiscuous, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. Beside its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, plays also a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium.<ref>PMID:17143272</ref>
+== 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/gx/3gxu_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=3gxu ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+EphA and EphB receptors preferentially bind ephrin-A and ephrin-B ligands, respectively, but EphA4 is exceptional for its ability to bind all ephrins. Here, we report the crystal structure of the EphA4 ligand-binding domain in complex with ephrin-B2, which represents the first structure of an EphA-ephrin-B interclass complex. A loose fit of the ephrin-B2 G-H loop in the EphA4 ligand-binding channel is consistent with a relatively weak binding affinity. Additional surface contacts also exist between EphA4 residues Gln(12) and Glu(14) and ephrin-B2. Mutation of Gln(12) and Glu(14) does not cause significant structural changes in EphA4 or changes in its affinity for ephrin-A ligands. However, the EphA4 mutant has approximately 10-fold reduced affinity for ephrin-B ligands, indicating that the surface contacts are critical for interclass but not intraclass ephrin binding. Thus, EphA4 uses different strategies to bind ephrin-A or ephrin-B ligands and achieve binding promiscuity. NMR characterization also suggests that the contacts of Gln(12) and Glu(14) with ephrin-B2 induce dynamic changes throughout the whole EphA4 ligand-binding domain. Our findings shed light on the distinctive features that enable the remarkable ligand binding promiscuity of EphA4 and suggest that diverse strategies are needed to effectively disrupt different Eph-ephrin complexes.
-===Crystal structure of Eph receptor and ephrin complex===
+Structural characterization of the EphA4-Ephrin-B2 complex reveals new features enabling Eph-ephrin binding promiscuity.,Qin H, Noberini R, Huan X, Shi J, Pasquale EB, Song J J Biol Chem. 2010 Jan 1;285(1):644-54. Epub 2009 Oct 29. PMID:19875447<ref>PMID:19875447</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3gxu" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_19875447}}, adds the Publication Abstract to the page
+*[[Ephrin|Ephrin]]
-(as it appears on PubMed at http://www.pubmed.gov), where 19875447 is the PubMed ID number.
+*[[Ephrin receptor 3D structures|Ephrin receptor 3D structures]]
--->
+== References ==
-{{ABSTRACT_PUBMED_19875447}}
+<references/>
+__TOC__
-==About this Structure==
+</StructureSection>
-[[3gxu]] 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=3GXU OCA].
-==Reference==
-<ref group="xtra">PMID:19875447</ref><ref group="xtra">PMID:18708347</ref><ref group="xtra">PMID:11780069</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Receptor protein-tyrosine kinase]]
+[[Category: Large Structures]]
-[[Category: Qin, H N.]]
+[[Category: Qin HN]]
-[[Category: Song, J X.]]
+[[Category: Song JX]]
-[[Category: Atp-binding]]
-[[Category: Complex structure]]
-[[Category: Developmental protein]]
-[[Category: Differentiation]]
-[[Category: Disulfide bond]]
-[[Category: Eph]]
-[[Category: Ephrin]]
-[[Category: Glycoprotein]]
-[[Category: Host-virus interaction]]
-[[Category: Kinase]]
-[[Category: Membrane]]
-[[Category: Neurogenesis]]
-[[Category: Nucleotide-binding]]
-[[Category: Phosphoprotein]]
-[[Category: Polymorphism]]
-[[Category: Receptor]]
-[[Category: Transferase]]
-[[Category: Transmembrane]]
-[[Category: Tyrosine-protein kinase]]