7czw

From Proteopedia

(Difference between revisions)

Current revision

S protein of SARS-CoV-2 in complex bound with P5A-2G7

Structural highlights

7czw is a 7 chain structure with sequence from Homo sapiens and Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.8Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HV461_HUMAN V region of the variable domain of immunoglobulin heavy chains that participates in the antigen recognition (PubMed:24600447). Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:20176268, PubMed:22158414). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:17576170, PubMed:20176268).^[1] ^[2] ^[3] ^[4] V9HW68_HUMAN

Publication Abstract from PubMed

Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus disease 2019 (COVID-19). We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable of disrupting proper interaction between the receptor binding domain (RBD) of the viral spike (S) protein and the receptor angiotensin converting enzyme 2 (ACE2). However, the structural basis for their potent neutralizing activity remains unclear. Here, we report cryo-EM structures of the ten most potent nAbs in their native full-length IgG-form or in both IgG-form and Fab-form bound to the trimeric S protein of SARS-CoV-2. The bivalent binding of the full-length IgG is found to associate with more RBDs in the "up" conformation than the monovalent binding of Fab, perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein. Comparison of a large number of nAbs identified common and unique structural features associated with their potent neutralizing activities. This work provides a structural basis for further understanding the mechanism of nAbs, especially through revealing the bivalent binding and its correlation with more potent neutralization and the shedding of S1 subunit.

Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies.,Yan R, Wang R, Ju B, Yu J, Zhang Y, Liu N, Wang J, Zhang Q, Chen P, Zhou B, Li Y, Shen Y, Zhang S, Tian L, Guo Y, Xia L, Zhong X, Cheng L, Ge X, Zhao J, Wang HW, Wang X, Zhang Z, Zhang L, Zhou Q Cell Res. 2021 May;31(5):517-525. doi: 10.1038/s41422-021-00487-9. Epub 2021 Mar , 17. PMID:33731853^[5]

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

References

↑ Teng G, Papavasiliou FN. Immunoglobulin somatic hypermutation. Annu Rev Genet. 2007;41:107-20. PMID:17576170 doi:http://dx.doi.org/10.1146/annurev.genet.41.110306.130340
↑ Schroeder HW Jr, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S41-52. doi:, 10.1016/j.jaci.2009.09.046. PMID:20176268 doi:http://dx.doi.org/10.1016/j.jaci.2009.09.046
↑ McHeyzer-Williams M, Okitsu S, Wang N, McHeyzer-Williams L. Molecular programming of B cell memory. Nat Rev Immunol. 2011 Dec 9;12(1):24-34. doi: 10.1038/nri3128. PMID:22158414 doi:http://dx.doi.org/10.1038/nri3128
↑ Lefranc MP. Immunoglobulin and T Cell Receptor Genes: IMGT((R)) and the Birth and Rise of Immunoinformatics. Front Immunol. 2014 Feb 5;5:22. doi: 10.3389/fimmu.2014.00022. eCollection 2014. PMID:24600447 doi:http://dx.doi.org/10.3389/fimmu.2014.00022
↑ Yan R, Wang R, Ju B, Yu J, Zhang Y, Liu N, Wang J, Zhang Q, Chen P, Zhou B, Li Y, Shen Y, Zhang S, Tian L, Guo Y, Xia L, Zhong X, Cheng L, Ge X, Zhao J, Wang HW, Wang X, Zhang Z, Zhang L, Zhou Q. Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies. Cell Res. 2021 May;31(5):517-525. PMID:33731853 doi:10.1038/s41422-021-00487-9

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/7czw"

@@ Line 1: / Line 1: @@
-====
+==S protein of SARS-CoV-2 in complex bound with P5A-2G7==
-<StructureSection load='7czw' size='340' side='right'caption='[[7czw]]' scene=''>
+<StructureSection load='7czw' size='340' side='right'caption='[[7czw]], [[Resolution|resolution]] 2.80&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'>[[7czw]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CZW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CZW 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=7czw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7czw OCA], [https://pdbe.org/7czw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7czw RCSB], [https://www.ebi.ac.uk/pdbsum/7czw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7czw ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.8&#8491;</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=7czw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7czw OCA], [https://pdbe.org/7czw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7czw RCSB], [https://www.ebi.ac.uk/pdbsum/7czw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7czw ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/HV461_HUMAN HV461_HUMAN] V region of the variable domain of immunoglobulin heavy chains that participates in the antigen recognition (PubMed:24600447). Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:20176268, PubMed:22158414). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:17576170, PubMed:20176268).<ref>PMID:17576170</ref> <ref>PMID:20176268</ref> <ref>PMID:22158414</ref> <ref>PMID:24600447</ref> [https://www.uniprot.org/uniprot/V9HW68_HUMAN V9HW68_HUMAN]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus disease 2019 (COVID-19). We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable of disrupting proper interaction between the receptor binding domain (RBD) of the viral spike (S) protein and the receptor angiotensin converting enzyme 2 (ACE2). However, the structural basis for their potent neutralizing activity remains unclear. Here, we report cryo-EM structures of the ten most potent nAbs in their native full-length IgG-form or in both IgG-form and Fab-form bound to the trimeric S protein of SARS-CoV-2. The bivalent binding of the full-length IgG is found to associate with more RBDs in the "up" conformation than the monovalent binding of Fab, perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein. Comparison of a large number of nAbs identified common and unique structural features associated with their potent neutralizing activities. This work provides a structural basis for further understanding the mechanism of nAbs, especially through revealing the bivalent binding and its correlation with more potent neutralization and the shedding of S1 subunit.
+Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies.,Yan R, Wang R, Ju B, Yu J, Zhang Y, Liu N, Wang J, Zhang Q, Chen P, Zhou B, Li Y, Shen Y, Zhang S, Tian L, Guo Y, Xia L, Zhong X, Cheng L, Ge X, Zhao J, Wang HW, Wang X, Zhang Z, Zhang L, Zhou Q Cell Res. 2021 May;31(5):517-525. doi: 10.1038/s41422-021-00487-9. Epub 2021 Mar , 17. PMID:33731853<ref>PMID:33731853</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 7czw" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Antibody 3D structures|Antibody 3D structures]]
+== References ==
+<references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Z-disk]]
+[[Category: Severe acute respiratory syndrome coronavirus 2]]
+[[Category: Li YN]]
+[[Category: Yan RH]]
+[[Category: Zhang YY]]
+[[Category: Zhou Q]]

7czw

From Proteopedia

Current revision

S protein of SARS-CoV-2 in complex bound with P5A-2G7

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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