4myv: Difference between revisions

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==Free HSV-2 gD structure==

== Structural highlights ==

<table><tr><td colspan='2'>~~[[4myv]] is a 2 chain structure.~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MYV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MYV FirstGlance]. <br>

<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MYV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MYV FirstGlance]. <br>

</td></tr>~~<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>~~

</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=4myv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4myv OCA], [https://pdbe.org/4myv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4myv RCSB], [https://www.ebi.ac.uk/pdbsum/4myv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4myv ProSAT]</span></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4myw|4myw]], [[3u82|3u82]], [[1l2g|1l2g]]</div></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=4myv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4myv OCA], [https://pdbe.org/4myv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4myv RCSB], [https://www.ebi.ac.uk/pdbsum/4myv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4myv ProSAT]</span></td></tr>

</table>

~~== Function ==~~

[[https://www.uniprot.org/uniprot/GD_HHV23 GD_HHV23]] Envelope glycoprotein that binds to the potential host cell entry receptors TNFRSF14/HVEM, PVRL1 and PVRL1. May trigger fusion with host membrane, by recruiting the fusion machinery composed of gB and gH/gL (By similarity).

~~<div style="background-color:#fffaf0;">~~

~~== Publication Abstract from PubMed ==~~

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are among the most prevalent human pathogens. Both viruses can recognize, via the surface envelope glycoprotein D (gD), human nectin-1 as a functional receptor. Previous studies have successfully elucidated the molecular basis of the binding between HSV-1 gD and nectin-1 by co-crystallography. Despite a high sequence identity between HSV-1 and -2 gDs, the atomic inter-molecule details for HSV-2-gD/nectin-1 interaction remain elusive. Here, we reported the crystal structures of both the unbound and the nectin-1-bound HSV-2 gD. The free gD structure expectedly comprises an IgV-like core and the surface-exposed terminal extensions as observed in its HSV-1 counterpart, but lacks traceable electron densities for a large portion of the terminal elements. These terminal residues were clearly traced in the complex structure as a definitive loop in the N-terminus and an alpha-helix in the C-terminus, thereby showing a conserved nectin-1-binding mode as reported for HSV-1 gD. The interface residues in nectin-1 were further mutated and tested for the gD-interaction by surface plasmon resonance. The resultant binding patterns were similar between HSV-1 and -2 gDs, further supporting a homologous receptor-binding basis by the two viruses for nectin-1. These data, together with a cell-based fusion assay showing a cross-inhibition of the gD/nectin-1 mediated cell-cell fusion by soluble HSV-1 and -2 gDs, provided solid structural and functional evidence that HSV-1/-2 recognizes nectin-1 via the same binding mode. Finally, we also demonstrated that nectin-1 I80 is an important residue involved in gD interaction. IMPORTANCE: Despite intensified studies, a detailed picture of the molecular features in the HSV-2-gD/nectin-1 interaction remains unavailable. Previous work focused on HSV-1 gD, which folds into an IgV-like core with large terminal extensions and utilizes the extension elements to engage nectin-1. Here, we reported the crystal structures of HSV-2 gD in both the free and the nectin-1-bound forms. The atomic inter-molecule details for HSV-2-gD/nectin-1 interaction were clearly presented. The observed binding mode is identical to that reported for its HSV-1 counterpart. This structural observation was further supported by our comparative functional assays showing that nectin-1 mutations similarly affect the ligand/receptor interaction of both virus gDs. Taken together, we provided comprehensive structural and functional data demonstrating a conserved receptor-binding mode between HSV-1 and -2 for nectin-1. Our results also indicate that the tropism-difference between the two viruses likely arises from other aspects rather than the gD/nectin-1 binding-features.

Crystal structure of HSV-2 gD bound to nectin-1 reveals a conserved mode of receptor recognition.,Lu G, Zhang N, Qi J, Li Y, Chen Z, Zheng C, Gao GF, Yan J J Virol. 2014 Sep 17. pii: JVI.01906-14. PMID:25231300<ref>PMID:25231300</ref>

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

~~</div>~~

~~<div class="pdbe-citations 4myv" style="background-color:#fffaf0;"></div>~~

==See Also==

*[[Glycoproteins B and D|Glycoproteins B and D]]

~~== References ==~~

~~<references/>~~

__TOC__

</StructureSection>

[[Category: Large Structures]]

[[Category: Chen, Z]]

[[Category: Chen Z]]

[[Category: Gao~~, G F~~]]

[[Category: Gao GF]]

[[Category: Li, Y]]

[[Category: Li Y]]

[[Category: Lu, G]]

[[Category: Lu G]]

[[Category: Qi, J]]

[[Category: Qi J]]

[[Category: Yan, J]]

[[Category: Yan J]]

[[Category: Zhang, N]]

[[Category: Zhang N]]

[[Category: Zheng, C]]

[[Category: Zheng C]]

~~[[Category: Hvem]]~~

~~[[Category: Igv-like core]]~~

~~[[Category: N-/c-terminal extension]]~~

~~[[Category: Nectin-1]]~~

~~[[Category: Receptor binding]]~~

~~[[Category: Viral protein]]~~

~~[[Category: Viral surface~~]]

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@@ Line 1: / Line 1: @@
 ==Free HSV-2 gD structure==
-<StructureSection load='4myv' size='340' side='right'caption='[[4myv]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+<StructureSection load='4myv' size='340' side='right'caption='[[4myv]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4myv]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MYV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MYV FirstGlance]. <br>
+<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MYV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MYV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</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=4myv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4myv OCA], [https://pdbe.org/4myv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4myv RCSB], [https://www.ebi.ac.uk/pdbsum/4myv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4myv ProSAT]</span></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4myw|4myw]], [[3u82|3u82]], [[1l2g|1l2g]]</div></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=4myv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4myv OCA], [https://pdbe.org/4myv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4myv RCSB], [https://www.ebi.ac.uk/pdbsum/4myv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4myv ProSAT]</span></td></tr>
 </table>
-== Function ==
-[[https://www.uniprot.org/uniprot/GD_HHV23 GD_HHV23]] Envelope glycoprotein that binds to the potential host cell entry receptors TNFRSF14/HVEM, PVRL1 and PVRL1. May trigger fusion with host membrane, by recruiting the fusion machinery composed of gB and gH/gL (By similarity).
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are among the most prevalent human pathogens. Both viruses can recognize, via the surface envelope glycoprotein D (gD), human nectin-1 as a functional receptor. Previous studies have successfully elucidated the molecular basis of the binding between HSV-1 gD and nectin-1 by co-crystallography. Despite a high sequence identity between HSV-1 and -2 gDs, the atomic inter-molecule details for HSV-2-gD/nectin-1 interaction remain elusive. Here, we reported the crystal structures of both the unbound and the nectin-1-bound HSV-2 gD. The free gD structure expectedly comprises an IgV-like core and the surface-exposed terminal extensions as observed in its HSV-1 counterpart, but lacks traceable electron densities for a large portion of the terminal elements. These terminal residues were clearly traced in the complex structure as a definitive loop in the N-terminus and an alpha-helix in the C-terminus, thereby showing a conserved nectin-1-binding mode as reported for HSV-1 gD. The interface residues in nectin-1 were further mutated and tested for the gD-interaction by surface plasmon resonance. The resultant binding patterns were similar between HSV-1 and -2 gDs, further supporting a homologous receptor-binding basis by the two viruses for nectin-1. These data, together with a cell-based fusion assay showing a cross-inhibition of the gD/nectin-1 mediated cell-cell fusion by soluble HSV-1 and -2 gDs, provided solid structural and functional evidence that HSV-1/-2 recognizes nectin-1 via the same binding mode. Finally, we also demonstrated that nectin-1 I80 is an important residue involved in gD interaction. IMPORTANCE: Despite intensified studies, a detailed picture of the molecular features in the HSV-2-gD/nectin-1 interaction remains unavailable. Previous work focused on HSV-1 gD, which folds into an IgV-like core with large terminal extensions and utilizes the extension elements to engage nectin-1. Here, we reported the crystal structures of HSV-2 gD in both the free and the nectin-1-bound forms. The atomic inter-molecule details for HSV-2-gD/nectin-1 interaction were clearly presented. The observed binding mode is identical to that reported for its HSV-1 counterpart. This structural observation was further supported by our comparative functional assays showing that nectin-1 mutations similarly affect the ligand/receptor interaction of both virus gDs. Taken together, we provided comprehensive structural and functional data demonstrating a conserved receptor-binding mode between HSV-1 and -2 for nectin-1. Our results also indicate that the tropism-difference between the two viruses likely arises from other aspects rather than the gD/nectin-1 binding-features.
-Crystal structure of HSV-2 gD bound to nectin-1 reveals a conserved mode of receptor recognition.,Lu G, Zhang N, Qi J, Li Y, Chen Z, Zheng C, Gao GF, Yan J J Virol. 2014 Sep 17. pii: JVI.01906-14. PMID:25231300<ref>PMID:25231300</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 4myv" style="background-color:#fffaf0;"></div>
 ==See Also==
 *[[Glycoproteins B and D|Glycoproteins B and D]]
-== References ==
-<references/>
 __TOC__
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Chen, Z]]
+[[Category: Chen Z]]
-[[Category: Gao, G F]]
+[[Category: Gao GF]]
-[[Category: Li, Y]]
+[[Category: Li Y]]
-[[Category: Lu, G]]
+[[Category: Lu G]]
-[[Category: Qi, J]]
+[[Category: Qi J]]
-[[Category: Yan, J]]
+[[Category: Yan J]]
-[[Category: Zhang, N]]
+[[Category: Zhang N]]
-[[Category: Zheng, C]]
+[[Category: Zheng C]]
-[[Category: Hvem]]
-[[Category: Igv-like core]]
-[[Category: N-/c-terminal extension]]
-[[Category: Nectin-1]]
-[[Category: Receptor binding]]
-[[Category: Viral protein]]
-[[Category: Viral surface]]