7zce

From Proteopedia

(Difference between revisions)

Current revision

SARS-CoV-2 Spike protein in complex with the single chain fragment scFv76

Structural highlights

7zce is a 6 chain structure with sequence from Escherichia virus T4, 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 3.5Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

WAC_BPT4 Chaperone responsible for attachment of long tail fibers to virus particle. Forms the fibrous structure on the neck of the virion called whiskers. During phage assembly, 6 fibritin molecules attach to each virion neck through their N-terminal domains, to form a collar with six fibers ('whiskers').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]^[1] ^[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]

Publication Abstract from PubMed

The uneven worldwide vaccination coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and emergence of variants escaping immunity call for broadly effective and easily deployable therapeutic agents. We have previously described the human single-chain scFv76 antibody, which recognizes SARS-CoV-2 Alpha, Beta, Gamma and Delta variants. We now show that scFv76 also neutralizes the infectivity and fusogenic activity of the Omicron BA.1 and BA.2 variants. Cryoelectron microscopy (cryo-EM) analysis reveals that scFv76 binds to a well-conserved SARS-CoV-2 spike epitope, providing the structural basis for its broad-spectrum activity. We demonstrate that nebulized scFv76 has therapeutic efficacy in a severe hACE2 transgenic mouse model of coronavirus disease 2019 (COVID-19) pneumonia, as shown by body weight and pulmonary viral load data. Counteraction of infection correlates with inhibition of lung inflammation, as observed by histopathology and expression of inflammatory cytokines and chemokines. Biomarkers of pulmonary endothelial damage were also significantly reduced in scFv76-treated mice. The results support use of nebulized scFv76 for COVID-19 induced by any SARS-CoV-2 variants that have emerged so far.

Spike mutation resilient scFv76 antibody counteracts SARS-CoV-2 lung damage upon aerosol delivery.,Milazzo FM, Chaves-Sanjuan A, Minenkova O, Santapaola D, Anastasi AM, Battistuzzi G, Chiapparino C, Rosi A, Merlo Pich E, Albertoni C, Marra E, Luberto L, Viollet C, Spagnoli LG, Riccio A, Rossi A, Santoro MG, Ballabio F, Paissoni C, Camilloni C, Bolognesi M, De Santis R Mol Ther. 2023 Feb 1;31(2):362-373. doi: 10.1016/j.ymthe.2022.09.010. Epub 2022 , Sep 15. PMID:36114671^[4]

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

References

↑ Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Graham BS, McLellan JS. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020 Feb 19. pii: science.abb2507. doi: 10.1126/science.abb2507. PMID:32075877 doi:http://dx.doi.org/10.1126/science.abb2507
↑ Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C, Pohlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Apr 16;181(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052. Epub 2020, Mar 5. PMID:32142651 doi:http://dx.doi.org/10.1016/j.cell.2020.02.052
↑ Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020 Mar 6. pii: S0092-8674(20)30262-2. doi: 10.1016/j.cell.2020.02.058. PMID:32155444 doi:http://dx.doi.org/10.1016/j.cell.2020.02.058
↑ Milazzo FM, Chaves-Sanjuan A, Minenkova O, Santapaola D, Anastasi AM, Battistuzzi G, Chiapparino C, Rosi A, Merlo Pich E, Albertoni C, Marra E, Luberto L, Viollet C, Spagnoli LG, Riccio A, Rossi A, Santoro MG, Ballabio F, Paissoni C, Camilloni C, Bolognesi M, De Santis R. Spike mutation resilient scFv76 antibody counteracts SARS-CoV-2 lung damage upon aerosol delivery. Mol Ther. 2023 Feb 1;31(2):362-373. PMID:36114671 doi:10.1016/j.ymthe.2022.09.010

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/7zce"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[7zce]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4], [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=7ZCE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZCE 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]] 3.5&#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=7zce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zce OCA], [https://pdbe.org/7zce PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zce RCSB], [https://www.ebi.ac.uk/pdbsum/7zce PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zce ProSAT]</span></td></tr>
 </table>
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 7zce" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Spike protein 3D structures|Spike protein 3D structures]]
 == References ==
 <references/>

7zce

From Proteopedia

Current revision

SARS-CoV-2 Spike protein in complex with the single chain fragment scFv76

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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