2hel

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[[Image:2hel.jpg|left|200px]]
 
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==Crystal structure of a mutant EphA4 kinase domain (Y742A)==
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The line below this paragraph, containing "STRUCTURE_2hel", creates the "Structure Box" on the page.
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<StructureSection load='2hel' size='340' side='right'caption='[[2hel]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2hel]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HEL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HEL FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.35&#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=2hel FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hel OCA], [https://pdbe.org/2hel PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hel RCSB], [https://www.ebi.ac.uk/pdbsum/2hel PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hel ProSAT]</span></td></tr>
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{{STRUCTURE_2hel| PDB=2hel | SCENE= }}
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/EPHA4_MOUSE EPHA4_MOUSE] 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:9789074</ref> <ref>PMID:15537875</ref> <ref>PMID:16802330</ref> <ref>PMID:16818734</ref> <ref>PMID:17719550</ref> <ref>PMID:18094260</ref> <ref>PMID:17143272</ref> <ref>PMID:17785183</ref> <ref>PMID:18403711</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/he/2hel_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=2hel ConSurf].
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<div style="clear:both"></div>
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'''Crystal structure of a mutant EphA4 kinase domain (Y742A)'''
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==See Also==
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*[[Ephrin receptor 3D structures|Ephrin receptor 3D structures]]
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== References ==
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==Overview==
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<references/>
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Eph receptor tyrosine kinases (RTKs) mediate numerous developmental processes. Their activity is regulated by auto-phosphorylation on two tyrosines within the juxtamembrane segment (JMS) immediately N-terminal to the kinase domain (KD). Here, we probe the molecular details of Eph kinase activation through mutational analysis, X-ray crystallography and NMR spectroscopy on auto-inhibited and active EphB2 and EphA4 fragments. We show that a Tyr750Ala gain-of-function mutation in the KD and JMS phosphorylation independently induce disorder of the JMS and its dissociation from the KD. Our X-ray analyses demonstrate that this occurs without major conformational changes to the KD and with only partial ordering of the KD activation segment. However, conformational exchange for helix alphaC in the N-terminal KD lobe and for the activation segment, coupled with increased inter-lobe dynamics, is observed upon kinase activation in our NMR analyses. Overall, our results suggest that a change in inter-lobe dynamics and the sampling of catalytically competent conformations for helix alphaC and the activation segment rather than a transition to a static active conformation underlies Eph RTK activation.
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Large Structures]]
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2HEL is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HEL OCA].
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==Reference==
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A change in conformational dynamics underlies the activation of Eph receptor tyrosine kinases., Wiesner S, Wybenga-Groot LE, Warner N, Lin H, Pawson T, Forman-Kay JD, Sicheri F, EMBO J. 2006 Oct 4;25(19):4686-96. Epub 2006 Sep 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16977320 16977320]
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[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Single protein]]
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[[Category: Pawson T]]
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[[Category: Pawson, T.]]
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[[Category: Sicheri F]]
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[[Category: Sicheri, F.]]
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[[Category: Wybenga-Groot LE]]
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[[Category: Wybenga-Groot, L E.]]
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[[Category: Activation]]
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[[Category: Tyr kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:11:51 2008''
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Current revision

Crystal structure of a mutant EphA4 kinase domain (Y742A)

PDB ID 2hel

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