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- PDB-9b82: Crystal structure of SARS-CoV-2 receptor binding domain in comple... -

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Basic information

Entry
Database: PDB / ID: 9b82
TitleCrystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibody COVA2-15
Components
  • COVA2-15 antibody heavy chain
  • COVA2-15 antibody light chain
  • Spike protein S1
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / Antibody / IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / membrane fusion / Attachment and Entry / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / receptor ligand activity / endocytosis involved in viral entry into host cell / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane
Similarity search - Function
Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, betacoronavirus / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus ...Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, betacoronavirus / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 2 (HR2) region profile. / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2
Similarity search - Domain/homology
Biological speciesSevere acute respiratory syndrome coronavirus 2
Homo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.38 Å
AuthorsYuan, M. / Zhu, X. / Wilson, I.A.
Funding support United States, 1items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationINV-004923 United States
CitationJournal: Plant Biotechnol J / Year: 2025
Title: Plant-produced SARS-CoV-2 antibody engineered towards enhanced potency and in vivo efficacy.
Authors: Steven W de Taeye / Loïc Faye / Bertrand Morel / Angela I Schriek / Jeffrey C Umotoy / Meng Yuan / Natalia A Kuzmina / Hannah L Turner / Xueyong Zhu / Clemens Grünwald-Gruber / Meliawati ...Authors: Steven W de Taeye / Loïc Faye / Bertrand Morel / Angela I Schriek / Jeffrey C Umotoy / Meng Yuan / Natalia A Kuzmina / Hannah L Turner / Xueyong Zhu / Clemens Grünwald-Gruber / Meliawati Poniman / Judith A Burger / Tom G Caniels / Anne-Catherine Fitchette / Réjean Desgagnés / Virginie Stordeur / Lucie Mirande / Guillaume Beauverger / Godelieve de Bree / Gabriel Ozorowski / Andrew B Ward / Ian A Wilson / Alexander Bukreyev / Rogier W Sanders / Louis-Philippe Vezina / Tim Beaumont / Marit J van Gils / Véronique Gomord /
Abstract: Prevention of severe COVID-19 disease by SARS-CoV-2 in high-risk patients, such as immuno-compromised individuals, can be achieved by administration of antibody prophylaxis, but producing antibodies ...Prevention of severe COVID-19 disease by SARS-CoV-2 in high-risk patients, such as immuno-compromised individuals, can be achieved by administration of antibody prophylaxis, but producing antibodies can be costly. Plant expression platforms allow substantial lower production costs compared to traditional bio-manufacturing platforms depending on mammalian cells in bioreactors. In this study, we describe the expression, production and purification of the originally human COVA2-15 antibody in plants. Our plant-produced mAbs demonstrated comparable neutralizing activity with COVA2-15 produced in mammalian cells. Furthermore, they exhibited similar capacity to prevent SARS-CoV-2 infection in a hamster model. To further enhance these biosimilars, we performed three glyco- and protein engineering techniques. First, to increase antibody half-life, we introduced YTE-mutation in the Fc tail; second, optimization of N-linked glycosylation by the addition of a C-terminal ER-retention motif (HDEL), and finally; production of mAb in plant production lines lacking β-1,2-xylosyltransferase and α-1,3-fucosyltransferase activities (FX-KO). These engineered biosimilars exhibited optimized glycosylation, enhanced phagocytosis and NK cell activation capacity compared to conventional plant-produced S15 and M15 biosimilars, in some cases outperforming mammalian cell produced COVA2-15. These engineered antibodies hold great potential for enhancing in vivo efficacy of mAb treatment against COVID-19 and provide a platform for the development of antibodies against other emerging viruses in a cost-effective manner.
History
DepositionMar 28, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 4, 2024Provider: repository / Type: Initial release
Revision 1.1Jan 8, 2025Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year / _citation_author.identifier_ORCID

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Spike protein S1
H: COVA2-15 antibody heavy chain
L: COVA2-15 antibody light chain
C: Spike protein S1
I: COVA2-15 antibody heavy chain
G: COVA2-15 antibody light chain
B: Spike protein S1
K: COVA2-15 antibody heavy chain
J: COVA2-15 antibody light chain
D: Spike protein S1
N: COVA2-15 antibody heavy chain
M: COVA2-15 antibody light chain
E: Spike protein S1
P: COVA2-15 antibody heavy chain
O: COVA2-15 antibody light chain
F: Spike protein S1
R: COVA2-15 antibody heavy chain
Q: COVA2-15 antibody light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)431,27524
Polymers429,94818
Non-polymers1,3276
Water00
1
A: Spike protein S1
H: COVA2-15 antibody heavy chain
L: COVA2-15 antibody light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)71,8794
Polymers71,6583
Non-polymers2211
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
C: Spike protein S1
I: COVA2-15 antibody heavy chain
G: COVA2-15 antibody light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)71,8794
Polymers71,6583
Non-polymers2211
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
B: Spike protein S1
K: COVA2-15 antibody heavy chain
J: COVA2-15 antibody light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)71,8794
Polymers71,6583
Non-polymers2211
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
D: Spike protein S1
N: COVA2-15 antibody heavy chain
M: COVA2-15 antibody light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)71,8794
Polymers71,6583
Non-polymers2211
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
5
E: Spike protein S1
P: COVA2-15 antibody heavy chain
O: COVA2-15 antibody light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)71,8794
Polymers71,6583
Non-polymers2211
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
6
F: Spike protein S1
R: COVA2-15 antibody heavy chain
Q: COVA2-15 antibody light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)71,8794
Polymers71,6583
Non-polymers2211
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)101.051, 218.660, 122.728
Angle α, β, γ (deg.)90.00, 112.34, 90.00
Int Tables number4
Space group name H-MP1211

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Components

#1: Protein
Spike protein S1


Mass: 23104.867 Da / Num. of mol.: 6 / Fragment: Receptor binding domain, UNP residues 333-530
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2
Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P0DTC2
#2: Antibody
COVA2-15 antibody heavy chain


Mass: 24360.172 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Mus musculus (house mouse)
#3: Antibody
COVA2-15 antibody light chain


Mass: 24192.900 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Mus musculus (house mouse)
#4: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 2.92 Å3/Da / Density % sol: 57.83 %
Crystal growTemperature: 293.15 K / Method: vapor diffusion, sitting drop
Details: 0.095 M sodium citrate, pH 5.6, 19% (v/v) 2-propanol, 5% (v/v) glycerol, and 19% (w/v) polyethylene glycol 4000

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 0.97934 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 11, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97934 Å / Relative weight: 1
ReflectionResolution: 3.38→50 Å / Num. obs: 68687 / % possible obs: 100 % / Redundancy: 6.8 % / CC1/2: 0.984 / CC star: 0.996 / Rmerge(I) obs: 0.208 / Rpim(I) all: 0.087 / Rrim(I) all: 0.226 / Χ2: 0.616 / Net I/σ(I): 3.1
Reflection shell

Diffraction-ID: 1 / % possible all: 100

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2CC starRpim(I) allRrim(I) allΧ2
3.4-3.466.81.32733720.6770.8980.5541.440.731
3.46-3.526.81.58134930.5610.8480.6531.7130.479
3.52-3.596.41.0433550.6220.8760.4441.1330.431
3.59-3.666.51.19434370.660.8920.5051.2980.541
3.66-3.7470.83234440.8690.9640.3410.90.728
3.74-3.8370.76434020.7850.9380.3110.8260.444
3.83-3.926.90.63934370.9570.9890.2680.6940.904
3.92-4.0370.55434070.9160.9780.2260.5990.465
4.03-4.156.90.33834260.9540.9880.1380.3650.456
4.15-4.286.50.2634410.9650.9910.110.2830.472
4.28-4.446.60.19734390.980.9950.0820.2130.5
4.44-4.6170.16634200.9860.9960.0680.1790.502
4.61-4.826.60.14234440.9880.9970.060.1540.525
4.82-5.0870.13734620.9890.9970.0560.1480.519
5.08-5.47.10.13134100.990.9970.0530.1420.558
5.4-5.8170.12734100.9910.9980.0520.1370.587
5.81-6.46.50.1234690.990.9970.0510.1310.605
6.4-7.326.70.09634540.9940.9980.040.1040.653
7.32-9.2170.06434550.9970.9990.0260.0690.797
9.21-506.40.05335100.9970.9990.0220.0571.432

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Processing

Software
NameVersionClassification
PHENIX(1.21rc1_5127: ???)refinement
HKL-2000data scaling
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 3.38→33.14 Å / SU ML: 0.58 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 31.19 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2951 3273 4.83 %
Rwork0.2417 --
obs0.2442 67804 98.73 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 3.38→33.14 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms29278 0 84 0 29362
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.002
X-RAY DIFFRACTIONf_angle_d0.493
X-RAY DIFFRACTIONf_dihedral_angle_d15.77110718
X-RAY DIFFRACTIONf_chiral_restr0.0424479
X-RAY DIFFRACTIONf_plane_restr0.0045303
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.38-3.430.36951580.38742647X-RAY DIFFRACTION95
3.43-3.480.42171470.3542764X-RAY DIFFRACTION98
3.48-3.540.29761170.31072791X-RAY DIFFRACTION98
3.54-3.60.35641580.30362779X-RAY DIFFRACTION97
3.6-3.670.39931370.36812736X-RAY DIFFRACTION99
3.67-3.740.34221480.31482810X-RAY DIFFRACTION98
3.74-3.810.37041540.30852776X-RAY DIFFRACTION98
3.81-3.90.41251310.32962807X-RAY DIFFRACTION98
3.9-3.990.33491450.30742773X-RAY DIFFRACTION99
3.99-4.090.32921470.26812813X-RAY DIFFRACTION99
4.09-4.20.30791630.25442821X-RAY DIFFRACTION99
4.2-4.320.2751310.24042784X-RAY DIFFRACTION99
4.32-4.460.29331440.232835X-RAY DIFFRACTION100
4.46-4.620.31331400.21612828X-RAY DIFFRACTION99
4.62-4.80.27421500.21572827X-RAY DIFFRACTION100
4.8-5.020.26011460.21972825X-RAY DIFFRACTION99
5.02-5.290.25061380.21242837X-RAY DIFFRACTION100
5.29-5.620.26121410.21242858X-RAY DIFFRACTION100
5.62-6.050.25791320.21542812X-RAY DIFFRACTION99
6.05-6.650.28341260.21682868X-RAY DIFFRACTION100
6.65-7.60.25721580.20922813X-RAY DIFFRACTION100
7.6-9.540.24411410.19752870X-RAY DIFFRACTION100
9.54-33.140.25991210.19582857X-RAY DIFFRACTION98

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