8hc3: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[8hc3]] 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=8HC3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HC3 FirstGlance]. <br>
<table><tr><td colspan='2'>[[8hc3]] 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=8HC3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HC3 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">Electron Microscopy, [[Resolution|Resolution]] 4.35&#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=8hc3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hc3 OCA], [https://pdbe.org/8hc3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hc3 RCSB], [https://www.ebi.ac.uk/pdbsum/8hc3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hc3 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=8hc3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hc3 OCA], [https://pdbe.org/8hc3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hc3 RCSB], [https://www.ebi.ac.uk/pdbsum/8hc3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hc3 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
<div style="background-color:#fffaf0;">
[https://www.uniprot.org/uniprot/SPIKE_SARS2 SPIKE_SARS2] attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). Uses also human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:32075877</ref> <ref>PMID:32142651</ref> <ref>PMID:32155444</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]
== Publication Abstract from PubMed ==
SARS-CoV-2 Omicron variants feature highly mutated spike proteins with extraordinary abilities in evading antibodies isolated earlier in the pandemic. Investigation of memory B cells from patients primarily with breakthrough infections with the Delta variant enables isolation of a number of neutralizing antibodies cross-reactive to heterologous variants of concern (VOCs) including Omicron variants (BA.1-BA.4). Structural studies identify altered complementarity determining region (CDR) amino acids and highly unusual heavy chain CDR2 insertions respectively in two representative cross-neutralizing antibodies-YB9-258 and YB13-292. These features are putatively introduced by somatic hypermutation and they are heavily involved in epitope recognition to broaden neutralization breadth. Previously, insertions/deletions were rarely reported for antiviral antibodies except for those induced by HIV-1 chronic infections. These data provide molecular mechanisms for cross-neutralization of heterologous SARS-CoV-2 variants by antibodies isolated from Delta variant infected patients with implications for future vaccination strategy.
 
Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants.,Yu H, Liu B, Zhang Y, Gao X, Wang Q, Xiang H, Peng X, Xie C, Wang Y, Hu P, Shi J, Shi Q, Zheng P, Feng C, Tang G, Liu X, Guo L, Lin X, Li J, Liu C, Huang Y, Yang N, Chen Q, Li Z, Su M, Yan Q, Pei R, Chen X, Liu L, Hu F, Liang D, Ke B, Ke C, Li F, He J, Wang M, Chen L, Xiong X, Tang X Nat Commun. 2023 Feb 24;14(1):1058. doi: 10.1038/s41467-023-36761-0. PMID:36828833<ref>PMID:36828833</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8hc3" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>

Latest revision as of 12:53, 9 October 2024

SARS-CoV-2 Omicron BA.1 spike trimer (6P) in complex with 2 YB9-258 Fabs (2 RBD up)SARS-CoV-2 Omicron BA.1 spike trimer (6P) in complex with 2 YB9-258 Fabs (2 RBD up)

Structural highlights

8hc3 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 4.35Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

SARS-CoV-2 Omicron variants feature highly mutated spike proteins with extraordinary abilities in evading antibodies isolated earlier in the pandemic. Investigation of memory B cells from patients primarily with breakthrough infections with the Delta variant enables isolation of a number of neutralizing antibodies cross-reactive to heterologous variants of concern (VOCs) including Omicron variants (BA.1-BA.4). Structural studies identify altered complementarity determining region (CDR) amino acids and highly unusual heavy chain CDR2 insertions respectively in two representative cross-neutralizing antibodies-YB9-258 and YB13-292. These features are putatively introduced by somatic hypermutation and they are heavily involved in epitope recognition to broaden neutralization breadth. Previously, insertions/deletions were rarely reported for antiviral antibodies except for those induced by HIV-1 chronic infections. These data provide molecular mechanisms for cross-neutralization of heterologous SARS-CoV-2 variants by antibodies isolated from Delta variant infected patients with implications for future vaccination strategy.

Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants.,Yu H, Liu B, Zhang Y, Gao X, Wang Q, Xiang H, Peng X, Xie C, Wang Y, Hu P, Shi J, Shi Q, Zheng P, Feng C, Tang G, Liu X, Guo L, Lin X, Li J, Liu C, Huang Y, Yang N, Chen Q, Li Z, Su M, Yan Q, Pei R, Chen X, Liu L, Hu F, Liang D, Ke B, Ke C, Li F, He J, Wang M, Chen L, Xiong X, Tang X Nat Commun. 2023 Feb 24;14(1):1058. doi: 10.1038/s41467-023-36761-0. PMID:36828833[1]

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

References

  1. Yu H, Liu B, Zhang Y, Gao X, Wang Q, Xiang H, Peng X, Xie C, Wang Y, Hu P, Shi J, Shi Q, Zheng P, Feng C, Tang G, Liu X, Guo L, Lin X, Li J, Liu C, Huang Y, Yang N, Chen Q, Li Z, Su M, Yan Q, Pei R, Chen X, Liu L, Hu F, Liang D, Ke B, Ke C, Li F, He J, Wang M, Chen L, Xiong X, Tang X. Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants. Nat Commun. 2023 Feb 24;14(1):1058. PMID:36828833 doi:10.1038/s41467-023-36761-0

8hc3, resolution 4.35Å

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