7x2m: Difference between revisions

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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7x2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x2m OCA], [https://pdbe.org/7x2m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x2m RCSB], [https://www.ebi.ac.uk/pdbsum/7x2m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x2m 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=7x2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x2m OCA], [https://pdbe.org/7x2m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x2m RCSB], [https://www.ebi.ac.uk/pdbsum/7x2m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x2m 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 ==
As SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we report on the identification of a special group of nanobodies from immunized alpaca with potency against diverse VOCs including Omicron subvariants BA.1, BA.2 and BA.4/5, SARS-CoV-1, and major sarbecoviruses. Crystal structure analysis of one representative nanobody, 3-2A2-4, discovers a highly conserved epitope located between the cryptic and the outer face of the receptor binding domain (RBD), distinctive from the receptor ACE2 binding site. Cryo-EM and biochemical evaluation reveal that 3-2A2-4 interferes structural alteration of RBD required for ACE2 binding. Passive delivery of 3-2A2-4 protects K18-hACE2 mice from infection of authentic SARS-CoV-2 Delta and Omicron. Identification of these unique nanobodies will inform the development of next generation antibody therapies and design of pan-sarbecovirus vaccines.
 
Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses.,Li M, Ren Y, Aw ZQ, Chen B, Yang Z, Lei Y, Cheng L, Liang Q, Hong J, Yang Y, Chen J, Wong YH, Wei J, Shan S, Zhang S, Ge J, Wang R, Dong JZ, Chen Y, Shi X, Zhang Q, Zhang Z, Chu JJH, Wang X, Zhang L Nat Commun. 2022 Dec 27;13(1):7957. doi: 10.1038/s41467-022-35642-2. PMID:36575191<ref>PMID:36575191</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7x2m" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Spike protein 3D structures|Spike protein 3D structures]]
== References ==
== References ==
<references/>
<references/>

Latest revision as of 12:20, 17 October 2024

Crystal structure of nanobody 1-2C7 with SARS-CoV-2 RBDCrystal structure of nanobody 1-2C7 with SARS-CoV-2 RBD

Structural highlights

7x2m is a 2 chain structure with sequence from Severe acute respiratory syndrome coronavirus 2 and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.8Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

As SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we report on the identification of a special group of nanobodies from immunized alpaca with potency against diverse VOCs including Omicron subvariants BA.1, BA.2 and BA.4/5, SARS-CoV-1, and major sarbecoviruses. Crystal structure analysis of one representative nanobody, 3-2A2-4, discovers a highly conserved epitope located between the cryptic and the outer face of the receptor binding domain (RBD), distinctive from the receptor ACE2 binding site. Cryo-EM and biochemical evaluation reveal that 3-2A2-4 interferes structural alteration of RBD required for ACE2 binding. Passive delivery of 3-2A2-4 protects K18-hACE2 mice from infection of authentic SARS-CoV-2 Delta and Omicron. Identification of these unique nanobodies will inform the development of next generation antibody therapies and design of pan-sarbecovirus vaccines.

Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses.,Li M, Ren Y, Aw ZQ, Chen B, Yang Z, Lei Y, Cheng L, Liang Q, Hong J, Yang Y, Chen J, Wong YH, Wei J, Shan S, Zhang S, Ge J, Wang R, Dong JZ, Chen Y, Shi X, Zhang Q, Zhang Z, Chu JJH, Wang X, Zhang L Nat Commun. 2022 Dec 27;13(1):7957. doi: 10.1038/s41467-022-35642-2. PMID:36575191[1]

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

See Also

References

  1. ↑ Li M, Ren Y, Aw ZQ, Chen B, Yang Z, Lei Y, Cheng L, Liang Q, Hong J, Yang Y, Chen J, Wong YH, Wei J, Shan S, Zhang S, Ge J, Wang R, Dong JZ, Chen Y, Shi X, Zhang Q, Zhang Z, Chu JJH, Wang X, Zhang L. Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses. Nat Commun. 2022 Dec 27;13(1):7957. PMID:36575191 doi:10.1038/s41467-022-35642-2

7x2m, resolution 1.80Å

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