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Structure paper

TitleThe antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants.
Journal, issue, pagesCell Host Microbe, Vol. 30, Issue 1, Page 53-68.e12, Year 2022
Publish dateJan 12, 2022
AuthorsChang Liu / Daming Zhou / Rungtiwa Nutalai / Helen M E Duyvesteyn / Aekkachai Tuekprakhon / Helen M Ginn / Wanwisa Dejnirattisai / Piyada Supasa / Alexander J Mentzer / Beibei Wang / James Brett Case / Yuguang Zhao / Donal T Skelly / Rita E Chen / Sile Ann Johnson / Thomas G Ritter / Chris Mason / Tariq Malik / Nigel Temperton / Neil G Paterson / Mark A Williams / David R Hall / Daniel K Clare / Andrew Howe / Philip J R Goulder / Elizabeth E Fry / Michael S Diamond / Juthathip Mongkolsapaya / Jingshan Ren / David I Stuart / Gavin R Screaton /
PubMed AbstractAlpha-B.1.1.7, Beta-B.1.351, Gamma-P.1, and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape ...Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1, and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is most antigenically separated from Delta. To understand this, we generated 674 mAbs from Beta-infected individuals and performed a detailed structure-function analysis of the 27 most potent mAbs: one binding the spike N-terminal domain (NTD), the rest the receptor-binding domain (RBD). Two of these RBD-binding mAbs recognize a neutralizing epitope conserved between SARS-CoV-1 and -2, while 18 target mutated residues in Beta: K417N, E484K, and N501Y. There is a major response to N501Y, including a public IgVH4-39 sequence, with E484K and K417N also targeted. Recognition of these key residues underscores why serum from Beta cases poorly neutralizes early pandemic and Delta viruses.
External linksCell Host Microbe / PubMed:34921776 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.7 - 4.9 Å
Structure data

13857

7q6e

EMDB-13857, PDB-7q6e:
Beta049 fab in complex with SARS-CoV2 beta-Spike glycoprotein, The Beta mAb response underscores the antigenic distance to other SARS-CoV-2 variants
Method: EM (single particle) / Resolution: 2.7 Å

13868

7q9f

EMDB-13868, PDB-7q9f:
Beta-50 fab in complex with SARS-CoV-2 beta-Spike glycoprotein
Method: EM (single particle) / Resolution: 3.6 Å

13869

7q9g

EMDB-13869, PDB-7q9g:
COVOX-222 fab in complex with SARS-CoV-2 beta-Spike glycoprotein
Method: EM (single particle) / Resolution: 3.3 Å

13870

7q9i

EMDB-13870, PDB-7q9i:
Beta-43 fab in complex with SARS-CoV-2 beta-Spike glycoprotein
Method: EM (single particle) / Resolution: 4.9 Å

13871

7q9j

EMDB-13871, PDB-7q9j:
Beta-26 fab in complex with SARS-CoV-2 beta-Spike glycoprotein
Method: EM (single particle) / Resolution: 4.0 Å

13872

7q9k

EMDB-13872, PDB-7q9k:
Beta-32 fab in complex with SARS-CoV-2 beta-Spike glycoprotein
Method: EM (single particle) / Resolution: 4.5 Å

13873

7q9m

EMDB-13873, PDB-7q9m:
Beta-53 fab in complex with SARS-CoV-2 beta-Spike glycoprotein
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-13874:
Beta-44 fab in complex with SARS-CoV-2 beta-Spike glycoprotein
Method: EM (single particle) / Resolution: 3.9 Å

13875

7q9p

EMDB-13875, PDB-7q9p:
Beta-06 fab in complex with SARS-CoV-2 beta-Spike glycoprotein
Method: EM (single particle) / Resolution: 4.5 Å

PDB-7pry:
Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with COVOX-45 and beta-6 Fabs
Method: X-RAY DIFFRACTION / Resolution: 3.1 Å

PDB-7prz:
Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with beta-22 Fabs
Method: X-RAY DIFFRACTION / Resolution: 3.2 Å

PDB-7ps0:
Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with beta-24 Fabs
Method: X-RAY DIFFRACTION / Resolution: 2.92 Å

PDB-7ps1:
Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-27 Fab
Method: X-RAY DIFFRACTION / Resolution: 2.4 Å

PDB-7ps2:
Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-29 and Beta-53 Fabs
Method: X-RAY DIFFRACTION / Resolution: 2.99 Å

PDB-7ps3:
Crystal structure of antibody Beta-32 Fab
Method: X-RAY DIFFRACTION / Resolution: 1.7 Å

PDB-7ps4:
Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-38
Method: X-RAY DIFFRACTION / Resolution: 1.94 Å

PDB-7ps5:
Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-47 Fab
Method: X-RAY DIFFRACTION / Resolution: 3.14 Å

PDB-7ps6:
Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-44 and Beta-54 Fabs
Method: X-RAY DIFFRACTION / Resolution: 2.26 Å

PDB-7ps7:
Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-40 Fab
Method: X-RAY DIFFRACTION / Resolution: 3.9 Å

PDB-7q0g:
Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-49 and FI-3A Fabs
Method: X-RAY DIFFRACTION / Resolution: 1.82 Å

PDB-7q0h:
Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-50 and Beta-54
Method: X-RAY DIFFRACTION / Resolution: 3.65 Å

PDB-7q0i:
Crystal structure of the N-terminal domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-43
Method: X-RAY DIFFRACTION / Resolution: 2.39 Å

Chemicals

ChemComp-SO4:
SULFATE ION

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-GOL:
GLYCEROL

ChemComp-CL:
Unknown entry

ChemComp-IOD:
IODIDE ION

ChemComp-PEG:
DI(HYDROXYETHYL)ETHER

ChemComp-HOH:
WATER

ChemComp-MLT:
D-MALATE

ChemComp-PG0:
2-(2-METHOXYETHOXY)ETHANOL / inhibitor, precipitant*YM

ChemComp-K:
Unknown entry

ChemComp-TAR:
D(-)-TARTARIC ACID

ChemComp-PO4:
PHOSPHATE ION

ChemComp-PG4:
TETRAETHYLENE GLYCOL / precipitant*YM

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / SARS-CoV-2 alpha variant / beta variant / gamma variant / delta variant / B.1.1.7 / B.1.351 / P.1 / B.1.617.2 / antibody / receptor-binding-domain / spike / neutralisation / VIRAL PROTEIN/IMMUNE SYSTEM / SARS-COV-2 B.1.1.7 (Alpha) VARIANT / B.1.351 (Beta) VARIANT / P.1 (Gamma) VARIANT / B.1.617.2 (Delta) VARIANT / IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM COMPLEX / RBD / N-terminal domain / NTD / SARS-CoV2 / glycoprotein / fab / B.1.135 / Complex / neutralising / convalescent sera

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