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6waq

From Proteopedia

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Current revision

Crystal structure of the SARS-CoV-1 RBD bound by the cross-reactive single-domain antibody SARS VHH-72

Structural highlights

6waq is a 4 chain structure with sequence from Lama glama and Severe acute 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 2.2Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SPIKE_SARS May down-regulate host tetherin (BST2) by lysosomal degradation, thereby counteracting its antiviral activity.^[1] Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 and CLEC4M/DC-SIGNR receptors and internalization of the virus into the endosomes of the host cell induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membrane fusion within endosomes.[HAMAP-Rule:MF_04099]^[2] ^[3] 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]^[4]

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^[5]

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

References

↑ Wang SM, Huang KJ, Wang CT. Severe acute respiratory syndrome coronavirus spike protein counteracts BST2-mediated restriction of virus-like particle release. J Med Virol. 2019 Oct;91(10):1743-1750. doi: 10.1002/jmv.25518. Epub 2019 Jul 10. PMID:31199522 doi:http://dx.doi.org/10.1002/jmv.25518
↑ Wong SK, Li W, Moore MJ, Choe H, Farzan M. A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J Biol Chem. 2004 Jan 30;279(5):3197-201. Epub 2003 Dec 11. PMID:14670965 doi:http://dx.doi.org/10.1074/jbc.C300520200
↑ Jeffers SA, Tusell SM, Gillim-Ross L, Hemmila EM, Achenbach JE, Babcock GJ, Thomas WD Jr, Thackray LB, Young MD, Mason RJ, Ambrosino DM, Wentworth DE, Demartini JC, Holmes KV. CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15748-53. doi:, 10.1073/pnas.0403812101. Epub 2004 Oct 20. PMID:15496474 doi:http://dx.doi.org/10.1073/pnas.0403812101
↑ Belouzard S, Chu VC, Whittaker GR. Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5871-6. doi:, 10.1073/pnas.0809524106. Epub 2009 Mar 24. PMID:19321428 doi:http://dx.doi.org/10.1073/pnas.0809524106
↑ 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/6waq"

Categories: Lama glama | Large Structures | Severe acute respiratory syndrome-related coronavirus | McLellan JS | Wrapp D

@@ Line 3: / Line 3: @@
 <StructureSection load='6waq' size='340' side='right'caption='[[6waq]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6waq]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhsa Cvhsa] and [http://en.wikipedia.org/wiki/Camelus_glama Camelus glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WAQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WAQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6waq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Lama_glama Lama glama] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome-related_coronavirus Severe acute respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WAQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WAQ 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]] 2.2&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">S, 2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=694009 CVHSA])</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'>[http://proteopedia.org/fgij/fg.htm?mol=6waq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6waq OCA], [http://pdbe.org/6waq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6waq RCSB], [http://www.ebi.ac.uk/pdbsum/6waq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6waq 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=6waq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6waq OCA], [https://pdbe.org/6waq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6waq RCSB], [https://www.ebi.ac.uk/pdbsum/6waq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6waq ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/SPIKE_CVHSA SPIKE_CVHSA]] S1 attaches the virion to the cell membrane by interacting with human ACE2 and CLEC4M/DC-SIGNR, initiating the infection. Binding to the receptor and internalization of the virus into the endosomes of the host cell probably induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.  S2 is 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.
+[https://www.uniprot.org/uniprot/SPIKE_SARS SPIKE_SARS] May down-regulate host tetherin (BST2) by lysosomal degradation, thereby counteracting its antiviral activity.<ref>PMID:31199522</ref>   Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 and CLEC4M/DC-SIGNR receptors and internalization of the virus into the endosomes of the host cell induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membrane fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:14670965</ref> <ref>PMID:15496474</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]<ref>PMID:19321428</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 6waq" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Antibody 3D structures|Antibody 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Camelus glama]]
+[[Category: Lama glama]]
-[[Category: Cvhsa]]
 [[Category: Large Structures]]
-[[Category: McLellan, J S]]
+[[Category: Severe acute respiratory syndrome-related coronavirus]]
-[[Category: Wrapp, D]]
+[[Category: McLellan JS]]
-[[Category: Nanobody]]
+[[Category: Wrapp D]]
-[[Category: Rbd]]
-[[Category: Sars-cov-1]]
-[[Category: Vhh]]
-[[Category: Viral protein]]
-[[Category: Viral protein-immune system complex]]

6waq

From Proteopedia

Current revision

Crystal structure of the SARS-CoV-1 RBD bound by the cross-reactive single-domain antibody SARS VHH-72

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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