6xe1

From Proteopedia

(Difference between revisions)

Current revision

Structure of SARS-CoV-2 spike protein receptor binding domain in complex with a potent neutralizing antibody, CV30 Fab

Structural highlights

6xe1 is a 3 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:	X-ray diffraction, Resolution 2.75Å
Ligands:	,
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

SARS-CoV-2 is a betacoronavirus virus responsible for the COVID-19 pandemic. Here, we determine the X-ray crystal structure of a potent neutralizing monoclonal antibody, CV30, isolated from a patient infected with SARS-CoV-2, in complex with the receptor binding domain. The structure reveals that CV30 binds to an epitope that overlaps with the human ACE2 receptor binding motif providing a structural basis for its neutralization. CV30 also induces shedding of the S1 subunit, indicating an additional mechanism of neutralization. A germline reversion of CV30 results in a substantial reduction in both binding affinity and neutralization potential indicating the minimal somatic mutation is needed for potently neutralizing antibodies against SARS-CoV-2.

Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation.,Hurlburt NK, Seydoux E, Wan YH, Edara VV, Stuart AB, Feng J, Suthar MS, McGuire AT, Stamatatos L, Pancera M Nat Commun. 2020 Oct 27;11(1):5413. doi: 10.1038/s41467-020-19231-9. PMID:33110068^[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
↑ Hurlburt NK, Seydoux E, Wan YH, Edara VV, Stuart AB, Feng J, Suthar MS, McGuire AT, Stamatatos L, Pancera M. Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation. Nat Commun. 2020 Oct 27;11(1):5413. PMID:33110068 doi:10.1038/s41467-020-19231-9

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/6xe1"

Categories: Homo sapiens | Large Structures | Severe acute respiratory syndrome coronavirus 2 | Hurlburt NK | Pancera M

@@ Line 12: / Line 12: @@
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
-SARS-CoV-2 is a betacoronavirus virus responsible for the COVID-19 pandemic. Here, we determined the X-ray crystal structure of a potent neutralizing monoclonal antibody, CV30, isolated from a patient infected with SARS-CoV-2, in complex with the receptor binding domain (RBD). The structure reveals CV30's epitope overlaps with the human ACE2 receptor binding site thus providing the structural basis for its neutralization by preventing ACE2 binding.
+SARS-CoV-2 is a betacoronavirus virus responsible for the COVID-19 pandemic. Here, we determine the X-ray crystal structure of a potent neutralizing monoclonal antibody, CV30, isolated from a patient infected with SARS-CoV-2, in complex with the receptor binding domain. The structure reveals that CV30 binds to an epitope that overlaps with the human ACE2 receptor binding motif providing a structural basis for its neutralization. CV30 also induces shedding of the S1 subunit, indicating an additional mechanism of neutralization. A germline reversion of CV30 results in a substantial reduction in both binding affinity and neutralization potential indicating the minimal somatic mutation is needed for potently neutralizing antibodies against SARS-CoV-2.
-Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation.,Hurlburt NK, Wan YH, Stuart AB, Feng J, McGuire AT, Stamatatos L, Pancera M bioRxiv. 2020 Jun 12:2020.06.12.148692. doi: 10.1101/2020.06.12.148692. Preprint. PMID:32577631<ref>PMID:32577631</ref>
+Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation.,Hurlburt NK, Seydoux E, Wan YH, Edara VV, Stuart AB, Feng J, Suthar MS, McGuire AT, Stamatatos L, Pancera M Nat Commun. 2020 Oct 27;11(1):5413. doi: 10.1038/s41467-020-19231-9. PMID:33110068<ref>PMID:33110068</ref>
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
@@ Line 22: / Line 22: @@
 ==See Also==
 *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
+*[[Spike protein 3D structures|Spike protein 3D structures]]
 == References ==
 <references/>

6xe1

From Proteopedia

Current revision

Structure of SARS-CoV-2 spike protein receptor binding domain in complex with a potent neutralizing antibody, CV30 Fab

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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