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1shx

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Revision as of 08:02, 14 March 2018

Ephrin A5 ligand structure

Structural highlights

1shx is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1shw
Gene:	EFNA5, EPLG7, LERK7, EPL7 (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[EFNA5_MOUSE] 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.^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Eph receptor tyrosine kinases (Ephs) function as molecular relays that interact with cell surface-bound ephrin ligands to direct the position of migrating cells. Structural studies revealed that, through two distinct contact surfaces on opposite sites of each protein, Eph and ephrin binding domains assemble into symmetric, circular heterotetramers. However, Eph signal initiation requires the assembly of higher order oligomers, suggesting additional points of contact. By screening a random library of EphA3 binding-compromised ephrin-A5 mutants, we have now determined ephrin-A5 residues that are essential for the assembly of high affinity EphA3 signaling complexes. In addition to the two interfaces predicted from the crystal structure of the homologous EphB2.ephrin-B2 complex, we identified a cluster of 10 residues on the ephrin-A5 E alpha-helix, the E-F loop, the underlying H beta-strand, as well as the nearby B-C loop, which define a distinct third surface required for oligomerization and activation of EphA3 signaling. Together with a corresponding third surface region identified recently outside of the minimal ephrin binding domain of EphA3, our findings provide experimental evidence for the essential contribution of three distinct protein-interaction interfaces to assemble functional EphA3 signaling complexes.

Three distinct molecular surfaces in ephrin-A5 are essential for a functional interaction with EphA3.,Day B, To C, Himanen JP, Smith FM, Nikolov DB, Boyd AW, Lackmann M J Biol Chem. 2005 Jul 15;280(28):26526-32. Epub 2005 May 18. PMID:15901737^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Park S, Sanchez MP. The Eek receptor, a member of the Eph family of tyrosine protein kinases, can be activated by three different Eph family ligands. Oncogene. 1997 Feb 6;14(5):533-42. PMID:9053851 doi:http://dx.doi.org/10.1038/sj.onc.1200857
↑ Holmberg J, Clarke DL, Frisen J. Regulation of repulsion versus adhesion by different splice forms of an Eph receptor. Nature. 2000 Nov 9;408(6809):203-6. PMID:11089974 doi:http://dx.doi.org/10.1038/35041577
↑ Konstantinova I, Nikolova G, Ohara-Imaizumi M, Meda P, Kucera T, Zarbalis K, Wurst W, Nagamatsu S, Lammert E. EphA-Ephrin-A-mediated beta cell communication regulates insulin secretion from pancreatic islets. Cell. 2007 Apr 20;129(2):359-70. PMID:17448994 doi:http://dx.doi.org/10.1016/j.cell.2007.02.044
↑ Cooper MA, Son AI, Komlos D, Sun Y, Kleiman NJ, Zhou R. Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to cataract. Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16620-5. doi:, 10.1073/pnas.0808987105. Epub 2008 Oct 23. PMID:18948590 doi:http://dx.doi.org/10.1073/pnas.0808987105
↑ Day B, To C, Himanen JP, Smith FM, Nikolov DB, Boyd AW, Lackmann M. Three distinct molecular surfaces in ephrin-A5 are essential for a functional interaction with EphA3. J Biol Chem. 2005 Jul 15;280(28):26526-32. Epub 2005 May 18. PMID:15901737 doi:10.1074/jbc.M504972200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1shx"

@@ Line 1: / Line 1: @@
 ==Ephrin A5 ligand structure==
 <StructureSection load='1shx' size='340' side='right' caption='[[1shx]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1shw|1shw]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EFNA5, EPLG7, LERK7, EPL7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=1shx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1shx OCA], [http://pdbe.org/1shx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1shx RCSB], [http://www.ebi.ac.uk/pdbsum/1shx PDBsum]</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=1shx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1shx OCA], [http://pdbe.org/1shx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1shx RCSB], [http://www.ebi.ac.uk/pdbsum/1shx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1shx ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sh/1shx_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sh/1shx_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1shx

From Proteopedia

Revision as of 08:02, 14 March 2018

Ephrin A5 ligand structure

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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