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| | ==Ghanaian henipavirus (Gh-M74a) attachment glycoprotein in complex with human ephrinB2== | | ==Ghanaian henipavirus (Gh-M74a) attachment glycoprotein in complex with human ephrinB2== |
| - | <StructureSection load='4uf7' size='340' side='right' caption='[[4uf7]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='4uf7' size='340' side='right'caption='[[4uf7]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4uf7]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UF7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UF7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4uf7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Ghana_virus Ghana virus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UF7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UF7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 1.7Å</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=4uf7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uf7 OCA], [http://pdbe.org/4uf7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uf7 RCSB], [http://www.ebi.ac.uk/pdbsum/4uf7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uf7 ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4uf7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uf7 OCA], [https://pdbe.org/4uf7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uf7 RCSB], [https://www.ebi.ac.uk/pdbsum/4uf7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uf7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/EFNB2_HUMAN EFNB2_HUMAN]] Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors 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. Binds to receptor tyrosine kinase including EPHA4, EPHA3 and EPHB4. Together with EPHB4 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. May play a role in constraining the orientation of longitudinally projecting axons.<ref>PMID:12734395</ref> | + | [https://www.uniprot.org/uniprot/EFNB2_HUMAN EFNB2_HUMAN] Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors 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. Binds to receptor tyrosine kinase including EPHA4, EPHA3 and EPHB4. Together with EPHB4 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. May play a role in constraining the orientation of longitudinally projecting axons.<ref>PMID:12734395</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 4uf7" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4uf7" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ephrin|Ephrin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ahmed, A A]] | + | [[Category: Ghana virus]] |
| - | [[Category: Beaty, S M]]
| + | [[Category: Homo sapiens]] |
| - | [[Category: Bowden, T A]]
| + | [[Category: Large Structures]] |
| - | [[Category: Lee, B]]
| + | [[Category: Ahmed AA]] |
| - | [[Category: Pernet, O]]
| + | [[Category: Beaty SM]] |
| - | [[Category: Zeltina, A]]
| + | [[Category: Bowden TA]] |
| - | [[Category: Gh-m74a]]
| + | [[Category: Lee B]] |
| - | [[Category: Ghv-g]]
| + | [[Category: Pernet O]] |
| - | [[Category: Glycoprotein]]
| + | [[Category: Zeltina A]] |
| - | [[Category: Hendra virus]]
| + | |
| - | [[Category: Hev-g]] | + | |
| - | [[Category: Hnv]] | + | |
| - | [[Category: Hnv-g]] | + | |
| - | [[Category: Nipah virus]] | + | |
| - | [[Category: Niv-g]] | + | |
| - | [[Category: Paramyxovirus]] | + | |
| - | [[Category: Viral attachment]] | + | |
| - | [[Category: Viral protein-immune system complex]] | + | |
| Structural highlights
Function
EFNB2_HUMAN Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors 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. Binds to receptor tyrosine kinase including EPHA4, EPHA3 and EPHB4. Together with EPHB4 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. May play a role in constraining the orientation of longitudinally projecting axons.[1]
Publication Abstract from PubMed
The discovery of African henipaviruses (HNVs) related to pathogenic Hendra virus (HeV) and Nipah virus (NiV) from Southeast Asia and Australia presents an open-ended health risk. Cell receptor use by emerging African HNVs at the stage of host-cell entry is a key parameter when considering the potential for spillover and infection of human populations. The attachment glycoprotein from a Ghanaian bat isolate (GhV-G) exhibits <30% sequence identity with Asiatic NiV-G/HeV-G. Here, through functional and structural analysis of GhV-G, we show how this African HNV targets the same human cell-surface receptor (ephrinB2) as the Asiatic HNVs. We first characterized this virus-receptor interaction crystallographically. Compared with extant HNV-G-ephrinB2 structures, there was significant structural variation in the six-bladed beta-propeller scaffold of the GhV-G receptor-binding domain, but not the Greek key fold of the bound ephrinB2. Analysis revealed a surprisingly conserved mode of ephrinB2 interaction that reflects an ongoing evolutionary constraint among geographically distal and phylogenetically divergent HNVs to maintain the functionality of ephrinB2 recognition during virus-host entry. Interestingly, unlike NiV-G/HeV-G, we could not detect binding of GhV-G to ephrinB3. Comparative structure-function analysis further revealed several distinguishing features of HNV-G function: a secondary ephrinB2 interaction site that contributes to more efficient ephrinB2-mediated entry in NiV-G relative to GhV-G and cognate residues at the very C terminus of GhV-G (absent in Asiatic HNV-Gs) that are vital for efficient receptor-induced fusion, but not receptor binding per se. These data provide molecular-level details for evaluating the likelihood of African HNVs to spill over into human populations.
Molecular recognition of human ephrinB2 cell surface receptor by an emergent African henipavirus.,Lee B, Pernet O, Ahmed AA, Zeltina A, Beaty SM, Bowden TA Proc Natl Acad Sci U S A. 2015 Mar 30. pii: 201501690. PMID:25825759[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fuller T, Korff T, Kilian A, Dandekar G, Augustin HG. Forward EphB4 signaling in endothelial cells controls cellular repulsion and segregation from ephrinB2 positive cells. J Cell Sci. 2003 Jun 15;116(Pt 12):2461-70. Epub 2003 May 6. PMID:12734395 doi:10.1242/jcs.00426
- ↑ Lee B, Pernet O, Ahmed AA, Zeltina A, Beaty SM, Bowden TA. Molecular recognition of human ephrinB2 cell surface receptor by an emergent African henipavirus. Proc Natl Acad Sci U S A. 2015 Mar 30. pii: 201501690. PMID:25825759 doi:http://dx.doi.org/10.1073/pnas.1501690112
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