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3zfx

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Revision as of 23:52, 4 August 2016

Crystal structure of EphB1

Structural highlights

3zfx is a 9 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3zew, 3zfm, 3zfy
Activity:	Receptor protein-tyrosine kinase, with EC number 2.7.10.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[EPHB1_HUMAN] 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. Cognate/functional ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During nervous system development, regulates retinal axon guidance redirecting ipsilaterally ventrotemporal retinal ganglion cells axons at the optic chiasm midline. This probably requires repulsive interaction with EFNB2. In the adult nervous system together with EFNB3, regulates chemotaxis, proliferation and polarity of the hippocampus neural progenitors. Beside its role in axon guidance plays also an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and synapse formation. May also regulate angiogenesis. More generally, may play a role in targeted cell migration and adhesion. Upon activation by EFNB1 and probably other ephrin-B ligands activates the MAPK/ERK and the JNK signaling cascades to regulate cell migration and adhesion respectively.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

The EphB receptors have key roles in cell morphology, adhesion, migration and invasion, and their aberrant action has been linked with the development and progression of many different tumour types. Their conflicting expression patterns in cancer tissues, combined with their high sequence and structural identity, present interesting challenges to those seeking to develop selective therapeutic molecules targeting this large receptor family. Here, we present the first structure of the EphB1 tyrosine kinase domain determined by X-ray crystallography to 2.5A. Our comparative crystalisation analysis of the human EphB family kinases has also yielded new crystal forms of the human EphB2 and EphB4 catalytic domains. Unable to crystallize the wild-type EphB3 kinase domain, we used rational engineering (based on our new structures of EphB1, EphB2 and EphB4) to identify a single point mutation which facilitated its crystallization and structure determination to 2.2A. This mutation also improved the soluble recombinant yield of this kinase within Escherichia coli, and increased both its intrinsic stability and catalytic turnover, without affecting its ligand-binding profile. The partial ordering of the activation loop in the EphB3 structure alludes to a potential cis-phosphorylation mechanism for the EphB kinases. With the kinase domain structures of all four catalytically competent human EphB receptors now determined, a picture begins to emerge of possible opportunities to produce EphB isozyme-selective kinase inhibitors for mechanistic studies and therapeutic applications.

Completing the structural family portrait of the human EphB tyrosine kinase domains.,Overman RC, Debreczeni JE, Truman CM, McAlister MS, Attwood TK Protein Sci. 2014 Feb 15. doi: 10.1002/pro.2445. PMID:24677421^[6]

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

References

↑ Stein E, Huynh-Do U, Lane AA, Cerretti DP, Daniel TO. Nck recruitment to Eph receptor, EphB1/ELK, couples ligand activation to c-Jun kinase. J Biol Chem. 1998 Jan 16;273(3):1303-8. PMID:9430661
↑ Stein E, Lane AA, Cerretti DP, Schoecklmann HO, Schroff AD, Van Etten RL, Daniel TO. Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses. Genes Dev. 1998 Mar 1;12(5):667-78. PMID:9499402
↑ Han DC, Shen TL, Miao H, Wang B, Guan JL. EphB1 associates with Grb7 and regulates cell migration. J Biol Chem. 2002 Nov 22;277(47):45655-61. Epub 2002 Sep 9. PMID:12223469 doi:10.1074/jbc.M203165200
↑ Vindis C, Cerretti DP, Daniel TO, Huynh-Do U. EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and promote chemotaxis. J Cell Biol. 2003 Aug 18;162(4):661-71. PMID:12925710 doi:http://dx.doi.org/10.1083/jcb.200302073
↑ Fasen K, Cerretti DP, Huynh-Do U. Ligand binding induces Cbl-dependent EphB1 receptor degradation through the lysosomal pathway. Traffic. 2008 Feb;9(2):251-66. Epub 2007 Dec 19. PMID:18034775 doi:http://dx.doi.org/10.1111/j.1600-0854.2007.00679.x
↑ Overman RC, Debreczeni JE, Truman CM, McAlister MS, Attwood TK. Completing the structural family portrait of the human EphB tyrosine kinase domains. Protein Sci. 2014 Feb 15. doi: 10.1002/pro.2445. PMID:24677421 doi:http://dx.doi.org/10.1002/pro.2445

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3zfx"

@@ Line 1: / Line 1: @@
 ==Crystal structure of EphB1==
 <StructureSection load='3zfx' size='340' side='right' caption='[[3zfx]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3zew|3zew]], [[3zfm|3zfm]], [[3zfy|3zfy]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </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=3zfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zfx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zfx RCSB], [http://www.ebi.ac.uk/pdbsum/3zfx 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=3zfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zfx OCA], [http://pdbe.org/3zfx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zfx RCSB], [http://www.ebi.ac.uk/pdbsum/3zfx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zfx ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3zfx" style="background-color:#fffaf0;"></div>
 ==See Also==

3zfx

From Proteopedia

Revision as of 23:52, 4 August 2016

Crystal structure of EphB1

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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