7x7v

From Proteopedia

(Difference between revisions)

Revision as of 10:28, 24 November 2022

Cryo-EM structure of SARS-CoV spike protein in complex with three nAbs X01, X10 and X17

Structural highlights

7x7v is a 7 chain structure with sequence from Mus musculus and Severe acute respiratory syndrome-related coronavirus. 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

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

Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of the potential candidates, we found that nAbs X01, X10, and X17 offer broad neutralizing potential against most variants of concern, with X17 further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-electron microscopy structures of the three antibodies together in complex with each of the spike proteins of the prototypical SARS-CoV, SARS-CoV-2, and Delta and Omicron variants of SARS-CoV-2 defined three nonoverlapping conserved epitopes on the receptor-binding domain. The triple-antibody mixture exhibited enhanced resistance to viral evasion and effective protection against infection of the Beta variant in hamsters. Our findings will aid the development of antibody therapeutics and broad vaccines against SARS-CoV-2 and its emerging variants.

The neutralizing breadth of antibodies targeting diverse conserved epitopes between SARS-CoV and SARS-CoV-2.,Xiong H, Sun H, Wang S, Yuan L, Liu L, Zhu Y, Zhang J, Huang Y, Qi R, Jiang Y, Ma J, Zhou M, Ma Y, Fu R, Yan S, Yue M, Wu Y, Wei M, Wang Y, Li T, Wang Y, Zheng Z, Yu H, Cheng T, Li S, Yuan Q, Zhang J, Guan Y, Zheng Q, Zhang T, Xia N Proc Natl Acad Sci U S A. 2022 Aug 23;119(34):e2204256119. doi: , 10.1073/pnas.2204256119. Epub 2022 Aug 16. PMID:35972965^[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
↑ Xiong H, Sun H, Wang S, Yuan L, Liu L, Zhu Y, Zhang J, Huang Y, Qi R, Jiang Y, Ma J, Zhou M, Ma Y, Fu R, Yan S, Yue M, Wu Y, Wei M, Wang Y, Li T, Wang Y, Zheng Z, Yu H, Cheng T, Li S, Yuan Q, Zhang J, Guan Y, Zheng Q, Zhang T, Xia N. The neutralizing breadth of antibodies targeting diverse conserved epitopes between SARS-CoV and SARS-CoV-2. Proc Natl Acad Sci U S A. 2022 Aug 23;119(34):e2204256119. doi: , 10.1073/pnas.2204256119. Epub 2022 Aug 16. PMID:35972965 doi:http://dx.doi.org/10.1073/pnas.2204256119

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/7x7v"

@@ Line 1: / Line 1: @@
-====
+==Cryo-EM structure of SARS-CoV spike protein in complex with three nAbs X01, X10 and X17==
-<StructureSection load='7x7v' size='340' side='right'caption='[[7x7v]]' scene=''>
+<StructureSection load='7x7v' size='340' side='right'caption='[[7x7v]], [[Resolution|resolution]] 3.83&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7x7v]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] 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=7X7V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7X7V FirstGlance]. <br>
-</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=7x7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x7v OCA], [https://pdbe.org/7x7v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x7v RCSB], [https://www.ebi.ac.uk/pdbsum/7x7v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x7v ProSAT]</span></td></tr>
+</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=7x7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x7v OCA], [https://pdbe.org/7x7v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x7v RCSB], [https://www.ebi.ac.uk/pdbsum/7x7v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x7v ProSAT]</span></td></tr>
 </table>
+== Function ==
+[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 ==
+Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of the potential candidates, we found that nAbs X01, X10, and X17 offer broad neutralizing potential against most variants of concern, with X17 further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-electron microscopy structures of the three antibodies together in complex with each of the spike proteins of the prototypical SARS-CoV, SARS-CoV-2, and Delta and Omicron variants of SARS-CoV-2 defined three nonoverlapping conserved epitopes on the receptor-binding domain. The triple-antibody mixture exhibited enhanced resistance to viral evasion and effective protection against infection of the Beta variant in hamsters. Our findings will aid the development of antibody therapeutics and broad vaccines against SARS-CoV-2 and its emerging variants.
+The neutralizing breadth of antibodies targeting diverse conserved epitopes between SARS-CoV and SARS-CoV-2.,Xiong H, Sun H, Wang S, Yuan L, Liu L, Zhu Y, Zhang J, Huang Y, Qi R, Jiang Y, Ma J, Zhou M, Ma Y, Fu R, Yan S, Yue M, Wu Y, Wei M, Wang Y, Li T, Wang Y, Zheng Z, Yu H, Cheng T, Li S, Yuan Q, Zhang J, Guan Y, Zheng Q, Zhang T, Xia N Proc Natl Acad Sci U S A. 2022 Aug 23;119(34):e2204256119. doi: , 10.1073/pnas.2204256119. Epub 2022 Aug 16. PMID:35972965<ref>PMID:35972965</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 7x7v" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Antibody 3D structures|Antibody 3D structures]]
+== References ==
+<references/>
 __TOC__
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Z-disk]]
+[[Category: Mus musculus]]
+[[Category: Severe acute respiratory syndrome-related coronavirus]]
+[[Category: Li S]]
+[[Category: Liu L]]
+[[Category: Sun H]]
+[[Category: Xia N]]
+[[Category: Zhang T]]
+[[Category: Zheng Q]]

7x7v

From Proteopedia

Revision as of 10:28, 24 November 2022

Cryo-EM structure of SARS-CoV spike protein in complex with three nAbs X01, X10 and X17

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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