6war

From Proteopedia

(Difference between revisions)

Revision as of 14:20, 18 October 2023

Crystal structure of the MERS-CoV RBD bound by the neutralizing single-domain antibody MERS VHH-55

Structural highlights

6war is a 16 chain structure with sequence from Lama glama and Middle East respiratory syndrome-related coronavirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.4Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SPIKE_MERS1 Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Interacts with host DPP4 to mediate virla entry.[HAMAP-Rule:MF_04099]^[1] Mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04099] Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099]

Publication Abstract from PubMed

Coronaviruses make use of a large envelope protein called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins play, they represent a vulnerable target for the development of therapeutics. Here, we describe the isolation of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs neutralize MERS-CoV or SARS-CoV-1 S pseudotyped viruses, respectively. Crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs interfere with receptor binding. We also show cross-reactivity between the SARS-CoV-1 S-directed VHH and SARS-CoV-2 S and demonstrate that this cross-reactive VHH neutralizes SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc-fusion. These data provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronavirus outbreaks.

Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies.,Wrapp D, De Vlieger D, Corbett KS, Torres GM, Wang N, Van Breedam W, Roose K, van Schie L, Hoffmann M, Pohlmann S, Graham BS, Callewaert N, Schepens B, Saelens X, McLellan JS Cell. 2020 Apr 29. pii: S0092-8674(20)30494-3. doi: 10.1016/j.cell.2020.04.031. PMID:32375025^[2]

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

References

↑ Raj VS, Mou H, Smits SL, Dekkers DH, Muller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013 Mar 14;495(7440):251-4. doi: 10.1038/nature12005. PMID:23486063 doi:http://dx.doi.org/10.1038/nature12005
↑ Wrapp D, De Vlieger D, Corbett KS, Torres GM, Wang N, Van Breedam W, Roose K, van Schie L, Hoffmann M, Pohlmann S, Graham BS, Callewaert N, Schepens B, Saelens X, McLellan JS. Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies. Cell. 2020 Apr 29. pii: S0092-8674(20)30494-3. doi: 10.1016/j.cell.2020.04.031. PMID:32375025 doi:http://dx.doi.org/10.1016/j.cell.2020.04.031

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6war"

@@ Line 3: / Line 3: @@
 <StructureSection load='6war' size='340' side='right'caption='[[6war]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6war]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Camelus_glama Camelus glama] and [http://en.wikipedia.org/wiki/Mers Mers]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WAR OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WAR FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6war]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Lama_glama Lama glama] and [https://en.wikipedia.org/wiki/Middle_East_respiratory_syndrome-related_coronavirus Middle East respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WAR 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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6war FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6war OCA], [http://pdbe.org/6war PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6war RCSB], [http://www.ebi.ac.uk/pdbsum/6war PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6war ProSAT]</span></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>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6war FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6war OCA], [https://pdbe.org/6war PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6war RCSB], [https://www.ebi.ac.uk/pdbsum/6war PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6war ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/SPIKE_MERS1 SPIKE_MERS1] Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Interacts with host DPP4 to mediate virla entry.[HAMAP-Rule:MF_04099]<ref>PMID:23486063</ref>   Mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04099]  Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 16: / Line 19: @@
 </div>
 <div class="pdbe-citations 6war" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Antibody 3D structures|Antibody 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Camelus glama]]
+[[Category: Lama glama]]
 [[Category: Large Structures]]
-[[Category: Mers]]
+[[Category: Middle East respiratory syndrome-related coronavirus]]
-[[Category: McLellan, J S]]
+[[Category: McLellan JS]]
-[[Category: Torres, G M]]
+[[Category: Torres GM]]
-[[Category: Wrapp, D]]
+[[Category: Wrapp D]]
-[[Category: Coronavirus]]
-[[Category: Mers-cov]]
-[[Category: Nanobody]]
-[[Category: Rbd]]
-[[Category: Viral protein]]
-[[Category: Viral protein-immune system complex]]

6war

From Proteopedia

Revision as of 14:20, 18 October 2023

Crystal structure of the MERS-CoV RBD bound by the neutralizing single-domain antibody MERS VHH-55

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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