|
|
| (4 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Crystal structure of EphB3== | | ==Crystal structure of EphB3== |
| - | <StructureSection load='3zfy' size='340' side='right' caption='[[3zfy]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='3zfy' size='340' side='right'caption='[[3zfy]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3zfy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZFY OCA]. <br> | + | <table><tr><td colspan='2'>[[3zfy]] 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=3ZFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZFY FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3zew|3zew]], [[3zfm|3zfm]], [[3zfx|3zfx]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></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=3zfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zfy OCA], [https://pdbe.org/3zfy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zfy RCSB], [https://www.ebi.ac.uk/pdbsum/3zfy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zfy ProSAT]</span></td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3zfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zfy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zfy RCSB], [http://www.ebi.ac.uk/pdbsum/3zfy PDBsum]</span></td></tr>
| + | </table> |
| - | <table> | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/EPHB3_HUMAN EPHB3_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. Generally has an overlapping and redundant function with EPHB2. Like EPHB2, functions in axon guidance during development regulating for instance the neurons forming the corpus callosum and the anterior commissure, 2 major interhemispheric connections between the temporal lobes of the cerebral cortex. 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 the formation of excitatory synapses. Controls other aspects of development through regulation of cell migration and positioning. This includes angiogenesis, palate development and thymic epithelium development for instance. Forward and reverse signaling through the EFNB2/EPHB3 complex also regulate migration and adhesion of cells that tubularize the urethra and septate the cloaca. Finally, plays an important role in intestinal epithelium differentiation segregating progenitor from differentiated cells in the crypt.<ref>PMID:15536074</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 13: |
Line 15: |
| | 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<ref>PMID:24677421</ref> | | 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<ref>PMID:24677421</ref> |
| | | | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3zfy" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ephrin receptor 3D structures|Ephrin receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Receptor protein-tyrosine kinase]] | + | [[Category: Large Structures]] |
| - | [[Category: Attwood, T K.]] | + | [[Category: Attwood TK]] |
| - | [[Category: Debreczeni, J E.]] | + | [[Category: Debreczeni JE]] |
| - | [[Category: McAlister, M.]] | + | [[Category: McAlister M]] |
| - | [[Category: Overman, R.]] | + | [[Category: Overman R]] |
| - | [[Category: Truman, C.]] | + | [[Category: Truman C]] |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
EPHB3_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. Generally has an overlapping and redundant function with EPHB2. Like EPHB2, functions in axon guidance during development regulating for instance the neurons forming the corpus callosum and the anterior commissure, 2 major interhemispheric connections between the temporal lobes of the cerebral cortex. 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 the formation of excitatory synapses. Controls other aspects of development through regulation of cell migration and positioning. This includes angiogenesis, palate development and thymic epithelium development for instance. Forward and reverse signaling through the EFNB2/EPHB3 complex also regulate migration and adhesion of cells that tubularize the urethra and septate the cloaca. Finally, plays an important role in intestinal epithelium differentiation segregating progenitor from differentiated cells in the crypt.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Miao H, Strebhardt K, Pasquale EB, Shen TL, Guan JL, Wang B. Inhibition of integrin-mediated cell adhesion but not directional cell migration requires catalytic activity of EphB3 receptor tyrosine kinase. Role of Rho family small GTPases. J Biol Chem. 2005 Jan 14;280(2):923-32. Epub 2004 Nov 9. PMID:15536074 doi:http://dx.doi.org/10.1074/jbc.M411383200
- ↑ 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
|
