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| | ==Crystal Structure of EphA5/SAMD5 Complex== | | ==Crystal Structure of EphA5/SAMD5 Complex== |
| - | <StructureSection load='5zrz' size='340' side='right' caption='[[5zrz]], [[Resolution|resolution]] 1.89Å' scene=''> | + | <StructureSection load='5zrz' size='340' side='right'caption='[[5zrz]], [[Resolution|resolution]] 1.89Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5zrz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZRZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZRZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5zrz]] 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=5ZRZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZRZ FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.89Å</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=5zrz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zrz OCA], [http://pdbe.org/5zrz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zrz RCSB], [http://www.ebi.ac.uk/pdbsum/5zrz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zrz ProSAT]</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=5zrz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zrz OCA], [https://pdbe.org/5zrz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zrz RCSB], [https://www.ebi.ac.uk/pdbsum/5zrz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zrz ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/EPHA5_MOUSE EPHA5_MOUSE]] Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A 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. Among GPI-anchored ephrin-A ligands, EFNA5 most probably constitutes the cognate/functional ligand for EPHA5. Functions as an axon guidance molecule during development and may be involved in the development of the retinotectal, entorhino-hippocampal and hippocamposeptal pathways. Together with EFNA5 plays also a role in synaptic plasticity in adult brain through regulation of synaptogenesis. In addition to its function in the nervous system, the interaction of EPHA5 with EFNA5 mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion.<ref>PMID:12124402</ref> <ref>PMID:17448994</ref> | + | [https://www.uniprot.org/uniprot/EPHA5_MOUSE EPHA5_MOUSE] Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A 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. Among GPI-anchored ephrin-A ligands, EFNA5 most probably constitutes the cognate/functional ligand for EPHA5. Functions as an axon guidance molecule during development and may be involved in the development of the retinotectal, entorhino-hippocampal and hippocamposeptal pathways. Together with EFNA5 plays also a role in synaptic plasticity in adult brain through regulation of synaptogenesis. In addition to its function in the nervous system, the interaction of EPHA5 with EFNA5 mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion.<ref>PMID:12124402</ref> <ref>PMID:17448994</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5zrz" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5zrz" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ephrin receptor 3D structures|Ephrin receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Receptor protein-tyrosine kinase]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, W]] | + | [[Category: Mus musculus]] |
| - | [[Category: Li, G]] | + | [[Category: Chen W]] |
| - | [[Category: Li, J]] | + | [[Category: Li G]] |
| - | [[Category: Liu, W]] | + | [[Category: Li J]] |
| - | [[Category: Shang, Y]] | + | [[Category: Liu W]] |
| - | [[Category: Wan, J]] | + | [[Category: Shang Y]] |
| - | [[Category: Wang, Y]] | + | [[Category: Wan J]] |
| - | [[Category: Zhang, M]] | + | [[Category: Wang Y]] |
| - | [[Category: Cell adhesion]]
| + | [[Category: Zhang M]] |
| - | [[Category: Cell signaling]]
| + | |
| - | [[Category: Heterodimer]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Sam domain]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Tyrosine-protein kinase]]
| + | |
| Structural highlights
Function
EPHA5_MOUSE Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A 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. Among GPI-anchored ephrin-A ligands, EFNA5 most probably constitutes the cognate/functional ligand for EPHA5. Functions as an axon guidance molecule during development and may be involved in the development of the retinotectal, entorhino-hippocampal and hippocamposeptal pathways. Together with EFNA5 plays also a role in synaptic plasticity in adult brain through regulation of synaptogenesis. In addition to its function in the nervous system, the interaction of EPHA5 with EFNA5 mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion.[1] [2]
Publication Abstract from PubMed
The Eph receptor tyrosine kinase (RTK) family is the largest subfamily of RTKs playing critical roles in many developmental processes such as tissue patterning, neurogenesis and neuronal circuit formation, angiogenesis, etc. How the 14 Eph proteins, via their highly similar cytoplasmic domains, can transmit diverse and sometimes opposite cellular signals upon engaging ephrins is a major unresolved question. Here we systematically investigated the bindings of each SAM domain of Eph receptors to the SAM domains from SHIP2 and Odin, and uncover a highly specific SAM-SAM interaction-mediated cytoplasmic Eph-effector binding pattern. Comparative X-ray crystallographic studies of several SAM-SAM heterodimer complexes, together with biochemical and cell biology experiments, not only revealed the exquisite specificity code governing Eph/effector interactions but also allowed us to identify SAMD5 as a new Eph binding partner. Finally, these Eph/effector SAM heterodimer structures can explain many Eph SAM mutations identified in patients suffering from cancers and other diseases.
Specific Eph receptor-cytoplasmic effector signaling mediated by SAM-SAM domain interactions.,Wang Y, Shang Y, Li J, Chen W, Li G, Wan J, Liu W, Zhang M Elife. 2018 May 11;7. pii: 35677. doi: 10.7554/eLife.35677. PMID:29749928[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yue Y, Chen ZY, Gale NW, Blair-Flynn J, Hu TJ, Yue X, Cooper M, Crockett DP, Yancopoulos GD, Tessarollo L, Zhou R. Mistargeting hippocampal axons by expression of a truncated Eph receptor. Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10777-82. doi:, 10.1073/pnas.162354599. Epub 2002 Jul 17. PMID:12124402 doi:http://dx.doi.org/10.1073/pnas.162354599
- ↑ 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
- ↑ Wang Y, Shang Y, Li J, Chen W, Li G, Wan J, Liu W, Zhang M. Specific Eph receptor-cytoplasmic effector signaling mediated by SAM-SAM domain interactions. Elife. 2018 May 11;7. pii: 35677. doi: 10.7554/eLife.35677. PMID:29749928 doi:http://dx.doi.org/10.7554/eLife.35677
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