7ly3

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of SARS-CoV-2 S NTD bound to S2M28 Fab

Structural highlights

7ly3 is a 6 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 3Å
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

The SARS-CoV-2 spike (S) glycoprotein contains an immunodominant receptor-binding domain (RBD) targeted by most neutralizing antibodies (Abs) in COVID-19 patient plasma. Little is known about neutralizing Abs binding to epitopes outside the RBD and their contribution to protection. Here, we describe 41 human monoclonal Abs (mAbs) derived from memory B cells, which recognize the SARS-CoV-2 S N-terminal domain (NTD) and show that a subset of them neutralize SARS-CoV-2 ultrapotently. We define an antigenic map of the SARS-CoV-2 NTD and identify a supersite (designated site i) recognized by all known NTD-specific neutralizing mAbs. These mAbs inhibit cell-to-cell fusion, activate effector functions, and protect Syrian hamsters from SARS-CoV-2 challenge, albeit selecting escape mutants in some animals. Indeed, several SARS-CoV-2 variants, including the B.1.1.7, B.1.351, and P.1 lineages, harbor frequent mutations within the NTD supersite, suggesting ongoing selective pressure and the importance of NTD-specific neutralizing mAbs for protective immunity and vaccine design.

N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2.,McCallum M, De Marco A, Lempp FA, Tortorici MA, Pinto D, Walls AC, Beltramello M, Chen A, Liu Z, Zatta F, Zepeda S, di Iulio J, Bowen JE, Montiel-Ruiz M, Zhou J, Rosen LE, Bianchi S, Guarino B, Fregni CS, Abdelnabi R, Foo SC, Rothlauf PW, Bloyet LM, Benigni F, Cameroni E, Neyts J, Riva A, Snell G, Telenti A, Whelan SPJ, Virgin HW, Corti D, Pizzuto MS, Veesler D Cell. 2021 Apr 29;184(9):2332-2347.e16. doi: 10.1016/j.cell.2021.03.028. Epub , 2021 Mar 16. PMID:33761326^[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
↑ McCallum M, De Marco A, Lempp FA, Tortorici MA, Pinto D, Walls AC, Beltramello M, Chen A, Liu Z, Zatta F, Zepeda S, di Iulio J, Bowen JE, Montiel-Ruiz M, Zhou J, Rosen LE, Bianchi S, Guarino B, Fregni CS, Abdelnabi R, Foo SC, Rothlauf PW, Bloyet LM, Benigni F, Cameroni E, Neyts J, Riva A, Snell G, Telenti A, Whelan SPJ, Virgin HW, Corti D, Pizzuto MS, Veesler D. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell. 2021 Apr 29;184(9):2332-2347.e16. PMID:33761326 doi:10.1016/j.cell.2021.03.028

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/7ly3"

Categories: Homo sapiens | Large Structures | Severe acute respiratory syndrome coronavirus 2 | McCallum M | Veesler D

@@ Line 5: / Line 5: @@
 <table><tr><td colspan='2'>[[7ly3]] is a 6 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=7LY3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LY3 FirstGlance]. <br>
 </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
-<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=XYL:D-XYLITOL'>XYL</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XYL:D-XYLITOL'>XYL</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=7ly3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ly3 OCA], [https://pdbe.org/7ly3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ly3 RCSB], [https://www.ebi.ac.uk/pdbsum/7ly3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ly3 ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 22: @@
 ==See Also==
 *[[Antibody 3D structures|Antibody 3D structures]]
+*[[Spike protein 3D structures|Spike protein 3D structures]]
 == References ==
 <references/>

7ly3

From Proteopedia

Current revision

Crystal structure of SARS-CoV-2 S NTD bound to S2M28 Fab

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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