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[[Image:1jpa.jpg|left|200px]]


{{Structure
==Crystal Structure of unphosphorylated EphB2 receptor tyrosine kinase and juxtamembrane region==
|PDB= 1jpa |SIZE=350|CAPTION= <scene name='initialview01'>1jpa</scene>, resolution 1.91&Aring;
<StructureSection load='1jpa' size='340' side='right'caption='[[1jpa]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>
<table><tr><td colspan='2'>[[1jpa]] is a 2 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=1JPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JPA FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.91&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1jpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jpa OCA], [https://pdbe.org/1jpa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jpa RCSB], [https://www.ebi.ac.uk/pdbsum/1jpa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jpa ProSAT]</span></td></tr>
|RELATEDENTRY=
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jpa OCA], [http://www.ebi.ac.uk/pdbsum/1jpa PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1jpa RCSB]</span>
== Function ==
}}
[https://www.uniprot.org/uniprot/EPHB2_MOUSE EPHB2_MOUSE] Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B 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. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. Beside axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor.<ref>PMID:8689685</ref> <ref>PMID:8947026</ref> <ref>PMID:9990854</ref> <ref>PMID:10839360</ref> <ref>PMID:14691139</ref> <ref>PMID:15223334</ref> <ref>PMID:21029865</ref>
 
== Evolutionary Conservation ==
'''Crystal Structure of unphosphorylated EphB2 receptor tyrosine kinase and juxtamembrane region'''
[[Image:Consurf_key_small.gif|200px|right]]
 
Check<jmol>
 
  <jmolCheckbox>
==Overview==
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jp/1jpa_consurf.spt"</scriptWhenChecked>
The Eph receptor tyrosine kinase family is regulated by autophosphorylation within the juxtamembrane region and the kinase activation segment. We have solved the X-ray crystal structure to 1.9 A resolution of an autoinhibited, unphosphorylated form of EphB2 comprised of the juxtamembrane region and the kinase domain. The structure, supported by mutagenesis data, reveals that the juxtamembrane segment adopts a helical conformation that distorts the small lobe of the kinase domain, and blocks the activation segment from attaining an activated conformation. Phosphorylation of conserved juxtamembrane tyrosines would relieve this autoinhibition by disturbing the association of the juxtamembrane segment with the kinase domain, while liberating phosphotyrosine sites for binding SH2 domains of target proteins. We propose that the autoinhibitory mechanism employed by EphB2 is a more general device through which receptor tyrosine kinases are controlled.
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 
    <text>to colour the structure by Evolutionary Conservation</text>
==About this Structure==
  </jmolCheckbox>
1JPA 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=1JPA OCA].  
</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=1jpa ConSurf].
 
<div style="clear:both"></div>
==Reference==
== References ==
Structural basis for autoinhibition of the Ephb2 receptor tyrosine kinase by the unphosphorylated juxtamembrane region., Wybenga-Groot LE, Baskin B, Ong SH, Tong J, Pawson T, Sicheri F, Cell. 2001 Sep 21;106(6):745-57. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11572780 11572780]
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Single protein]]
[[Category: Pawson T]]
[[Category: Pawson, T.]]
[[Category: Sicheri F]]
[[Category: Sicheri, F.]]
[[Category: Wybenga-Groot LE]]
[[Category: Wybenga-Groot, L E.]]
[[Category: autoinhibited]]
[[Category: juxtamembrane]]
[[Category: receptor tyrosine kinase]]
[[Category: unphosphorylated]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:36:54 2008''

Latest revision as of 10:41, 7 February 2024

Crystal Structure of unphosphorylated EphB2 receptor tyrosine kinase and juxtamembrane regionCrystal Structure of unphosphorylated EphB2 receptor tyrosine kinase and juxtamembrane region

Structural highlights

1jpa is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.91Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

EPHB2_MOUSE Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B 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. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. Beside axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor.[1] [2] [3] [4] [5] [6] [7]

Evolutionary Conservation

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

References

  1. ↑ Henkemeyer M, Orioli D, Henderson JT, Saxton TM, Roder J, Pawson T, Klein R. Nuk controls pathfinding of commissural axons in the mammalian central nervous system. Cell. 1996 Jul 12;86(1):35-46. PMID:8689685
  2. ↑ Orioli D, Henkemeyer M, Lemke G, Klein R, Pawson T. Sek4 and Nuk receptors cooperate in guidance of commissural axons and in palate formation. EMBO J. 1996 Nov 15;15(22):6035-49. PMID:8947026
  3. ↑ Adams RH, Wilkinson GA, Weiss C, Diella F, Gale NW, Deutsch U, Risau W, Klein R. Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev. 1999 Feb 1;13(3):295-306. PMID:9990854
  4. ↑ Cowan CA, Yokoyama N, Bianchi LM, Henkemeyer M, Fritzsch B. EphB2 guides axons at the midline and is necessary for normal vestibular function. Neuron. 2000 May;26(2):417-30. PMID:10839360
  5. ↑ Henkemeyer M, Itkis OS, Ngo M, Hickmott PW, Ethell IM. Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus. J Cell Biol. 2003 Dec 22;163(6):1313-26. PMID:14691139 doi:http://dx.doi.org/10.1083/jcb.200306033
  6. ↑ Dravis C, Yokoyama N, Chumley MJ, Cowan CA, Silvany RE, Shay J, Baker LA, Henkemeyer M. Bidirectional signaling mediated by ephrin-B2 and EphB2 controls urorectal development. Dev Biol. 2004 Jul 15;271(2):272-90. PMID:15223334 doi:http://dx.doi.org/10.1016/j.ydbio.2004.03.027
  7. ↑ Margolis SS, Salogiannis J, Lipton DM, Mandel-Brehm C, Wills ZP, Mardinly AR, Hu L, Greer PL, Bikoff JB, Ho HY, Soskis MJ, Sahin M, Greenberg ME. EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation. Cell. 2010 Oct 29;143(3):442-55. doi: 10.1016/j.cell.2010.09.038. PMID:21029865 doi:http://dx.doi.org/10.1016/j.cell.2010.09.038

1jpa, resolution 1.91Å

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