8tm1

From Proteopedia

(Difference between revisions)

Current revision

Antibody N3-1 bound to RBDs in the up and down conformations

Structural highlights

8tm1 is a 4 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 2.79Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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 ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight into mutations enabling immune escape. Understanding how these mutations affect the dynamics of antibody-antigen interactions is crucial to the development of broadly protective antibodies and vaccines. Here we report the characterization of a potent neutralizing antibody (N3-1) identified from a COVID-19 patient during the first disease wave. Cryogenic electron microscopy revealed a quaternary binding mode that enables direct interactions with all three receptor-binding domains of the spike protein trimer, resulting in extraordinary avidity and potent neutralization of all major variants of concern until the emergence of Omicron. Structure-based rational design of N3-1 mutants improved binding to all Omicron variants but only partially restored neutralization of the conformationally distinct Omicron BA.1. This study provides new insights into immune evasion through changes in spike protein dynamics and highlights considerations for future conformationally biased multivalent vaccine designs.

SARS-COV-2 Omicron variants conformationally escape a rare quaternary antibody binding mode.,Goike J, Hsieh CL, Horton AP, Gardner EC, Zhou L, Bartzoka F, Wang N, Javanmardi K, Herbert A, Abbassi S, Xie X, Xia H, Shi PY, Renberg R, Segall-Shapiro TH, Terrace CI, Wu W, Shroff R, Byrom M, Ellington AD, Marcotte EM, Musser JM, Kuchipudi SV, Kapur V, Georgiou G, Weaver SC, Dye JM, Boutz DR, McLellan JS, Gollihar JD Commun Biol. 2023 Dec 11;6(1):1250. doi: 10.1038/s42003-023-05649-6. PMID:38082099^[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
↑ Goike J, Hsieh CL, Horton AP, Gardner EC, Zhou L, Bartzoka F, Wang N, Javanmardi K, Herbert A, Abbassi S, Xie X, Xia H, Shi PY, Renberg R, Segall-Shapiro TH, Terrace CI, Wu W, Shroff R, Byrom M, Ellington AD, Marcotte EM, Musser JM, Kuchipudi SV, Kapur V, Georgiou G, Weaver SC, Dye JM, Boutz DR, McLellan JS, Gollihar JD. SARS-COV-2 Omicron variants conformationally escape a rare quaternary antibody binding mode. Commun Biol. 2023 Dec 11;6(1):1250. PMID:38082099 doi:10.1038/s42003-023-05649-6

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8tm1"

Categories: Homo sapiens | Large Structures | Severe acute respiratory syndrome coronavirus 2 | Hsieh C-L | McLellan JS

@@ Line 3: / Line 3: @@
 <StructureSection load='8tm1' size='340' side='right'caption='[[8tm1]], [[Resolution|resolution]] 2.79&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[8tm1]] is a 4 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]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=7six 7six]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8TM1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TM1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[8tm1]] is a 4 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=8TM1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TM1 FirstGlance]. <br>
 </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.79&#8491;</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=8tm1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8tm1 OCA], [https://pdbe.org/8tm1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8tm1 RCSB], [https://www.ebi.ac.uk/pdbsum/8tm1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8tm1 ProSAT]</span></td></tr>

8tm1

From Proteopedia

Current revision

Antibody N3-1 bound to RBDs in the up and down conformations

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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