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4uf7

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Revision as of 07:03, 28 February 2018

Ghanaian henipavirus (Gh-M74a) attachment glycoprotein in complex with human ephrinB2

Structural highlights

4uf7 is a 4 chain structure with sequence from Bat paramyxovirus eid_hel/gh-m74a/gha/2009 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4uf7"

@@ Line 3: / Line 3: @@
 <StructureSection load='4uf7' size='340' side='right' caption='[[4uf7]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == 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 [http://en.wikipedia.org/wiki/Bat_paramyxovirus_eid_hel/gh-m74a/gha/2009 Bat paramyxovirus eid_hel/gh-m74a/gha/2009] and [http://en.wikipedia.org/wiki/Human Human]. 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>
 </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>
 <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>
@@ Line 22: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Bat paramyxovirus eid_hel/gh-m74a/gha/2009]]
+[[Category: Human]]
 [[Category: Ahmed, A A]]
 [[Category: Beaty, S M]]

4uf7

From Proteopedia

Revision as of 07:03, 28 February 2018

Ghanaian henipavirus (Gh-M74a) attachment glycoprotein in complex with human ephrinB2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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