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- PDB-7z0y: THSC20.HVTR04 Fab bound to SARS-CoV-2 Receptor Binding Domain -

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Basic information

Entry
Database: PDB / ID: 7z0y
TitleTHSC20.HVTR04 Fab bound to SARS-CoV-2 Receptor Binding Domain
Components
  • (THSC20.HVTR04 Fab ...) x 2
  • Spike protein S1
KeywordsANTIVIRAL PROTEIN / IMMUNE SYSTEM / Neutralizing antibody / SARS-CoV-2 / Spike / RBD
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 / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / host cell surface receptor binding / 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 / membrane / identical protein binding / 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 / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike glycoprotein, betacoronavirus / 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 ...Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike glycoprotein, betacoronavirus / 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 2 (HR2) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2 / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
Severe acute respiratory syndrome coronavirus 2
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.95 Å
AuthorsWibmer, C.K.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/John E. Fogarty International Center (NIH/FIC)3R21TW011454-02S1 United States
Citation
Journal: PLoS Pathog / Year: 2022
Title: A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 Delta variant.
Authors: Nitin Hingankar / Suprit Deshpande / Payel Das / Zaigham Abbas Rizvi / Constantinos Kurt Wibmer / Poppy Mashilo / Mohammed Yousuf Ansari / Alison Burns / Shawn Barman / Fangzhu Zhao / Sohini ...Authors: Nitin Hingankar / Suprit Deshpande / Payel Das / Zaigham Abbas Rizvi / Constantinos Kurt Wibmer / Poppy Mashilo / Mohammed Yousuf Ansari / Alison Burns / Shawn Barman / Fangzhu Zhao / Sohini Mukherjee / Jonathan L Torres / Souvick Chattopadhyay / Farha Mehdi / Jyoti Sutar / Deepak Kumar Rathore / Kamal Pargai / Janmejay Singh / Sudipta Sonar / Kamini Jakhar / Jyotsna Dandotiya / Sankar Bhattacharyya / Shailendra Mani / Sweety Samal / Savita Singh / Pallavi Kshetrapal / Ramachandran Thiruvengadam / Gaurav Batra / Guruprasad Medigeshi / Andrew B Ward / Shinjini Bhatnagar / Amit Awasthi / Devin Sok / Jayanta Bhattacharya /
Abstract: Although efficacious vaccines have significantly reduced the morbidity and mortality of COVID-19, there remains an unmet medical need for treatment options, which monoclonal antibodies (mAbs) can ...Although efficacious vaccines have significantly reduced the morbidity and mortality of COVID-19, there remains an unmet medical need for treatment options, which monoclonal antibodies (mAbs) can potentially fill. This unmet need is exacerbated by the emergence and spread of SARS-CoV-2 variants of concern (VOCs) that have shown some resistance to vaccine responses. Here we report the isolation of five neutralizing mAbs from an Indian convalescent donor, out of which two (THSC20.HVTR04 and THSC20.HVTR26) showed potent neutralization of SARS-CoV-2 VOCs at picomolar concentrations, including the Delta variant (B.1.617.2). One of these (THSC20.HVTR26) also retained activity against the Omicron variant. These two mAbs target non-overlapping epitopes on the receptor-binding domain (RBD) of the spike protein and prevent virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Furthermore, the mAb cocktail demonstrated protection against the Delta variant at low antibody doses when passively administered in the K18 hACE2 transgenic mice model, highlighting their potential as a cocktail for prophylactic and therapeutic applications. Developing the capacity to rapidly discover and develop mAbs effective against highly transmissible pathogens like coronaviruses at a local level, especially in a low- and middle-income country (LMIC) such as India, will enable prompt responses to future pandemics as an important component of global pandemic preparedness.
#1: Journal: Biorxiv / Year: 2021
Title: A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 delta variant
Authors: Hingankar, N. / Deshpande, S. / Das, P. / Rizvi, Z.A. / Burns, A. / Barman, S. / Zhao, F. / Ansari, M.Y. / Mukherjee, S. / Torres, J.L. / Chattopadhyay, S. / Mehdi, F. / Sutar, J. / Rathore, ...Authors: Hingankar, N. / Deshpande, S. / Das, P. / Rizvi, Z.A. / Burns, A. / Barman, S. / Zhao, F. / Ansari, M.Y. / Mukherjee, S. / Torres, J.L. / Chattopadhyay, S. / Mehdi, F. / Sutar, J. / Rathore, D.K. / Pargai, K. / Singh, J. / Sonar, S. / Jakhar, K. / Bhattacharyya, S. / Mani, S. / Singh, S. / Dandotiya, J. / Kshetrapal, P. / Thiruvengadam, R. / Batra, G. / Medigeshi, G. / Ward, A.B. / Bhatnagar, S. / Awasthi, A. / Sok, D. / Bhattacharya, J.
History
DepositionFeb 23, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 13, 2022Provider: repository / Type: Initial release
Revision 1.1May 11, 2022Group: Database references / Source and taxonomy / Category: citation / citation_author / entity_src_gen
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.year / _citation_author.identifier_ORCID / _entity_src_gen.gene_src_common_name
Revision 1.2May 1, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / pdbx_initial_refinement_model
Item: _citation.journal_id_ISSN

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
H: THSC20.HVTR04 Fab heavy chain
L: THSC20.HVTR04 Fab light chain
R: Spike protein S1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)71,2306
Polymers70,4683
Non-polymers7633
Water1,17165
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)126.157, 126.157, 167.454
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number96
Space group name H-MP43212
Components on special symmetry positions
IDModelComponents
11R-729-

HOH

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Components

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Antibody , 2 types, 2 molecules HL

#1: Antibody THSC20.HVTR04 Fab heavy chain


Mass: 24848.957 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: Donor THSC20 / Source: (gene. exp.) Homo sapiens (human) / Tissue: Blood / Cell: B cell / Plasmid: pcDNA3.4 / Cell line (production host): Expi293 / Production host: Homo sapiens (human)
#2: Antibody THSC20.HVTR04 Fab light chain


Mass: 22602.953 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: Donor THSC20 / Source: (gene. exp.) Homo sapiens (human) / Tissue: Blood / Cell: B cell / Plasmid: pcDNA3.4 / Cell line (production host): Expi293 / Production host: Homo sapiens (human)

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Protein / Sugars , 2 types, 2 molecules R

#3: Protein Spike protein S1


Mass: 23015.803 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: Donor THSC20
Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2
Tissue: Blood / Cell: B cell / Gene: S, 2 / Variant: None / Plasmid: pcDNA3.4 / Cell line (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2
#4: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 570.542 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4[LFucpa1-6]DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1221m-1a_1-5]/1-1-2/a4-b1_a6-c1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}[(6+1)][a-L-Fucp]{}}LINUCSPDB-CARE

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Non-polymers , 2 types, 67 molecules

#5: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 65 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestN

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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: 4.73 Å3/Da / Density % sol: 73.97 %
Crystal growTemperature: 293 K / Method: vapor diffusion / pH: 6.5
Details: 1.5M ammonium sulfate, 12%(v/v) isopropanol, 0.1M imidazole HCl pH 6.5

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9795 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Nov 24, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.95→50 Å / Num. obs: 23099 / % possible obs: 78 % / Redundancy: 2 % / Biso Wilson estimate: 63.13 Å2 / CC1/2: 0.991 / Rmerge(I) obs: 0.05634 / Rpim(I) all: 0.05634 / Rrim(I) all: 0.07968 / Net I/σ(I): 17.4
Reflection shellResolution: 2.95→3.05 Å / Redundancy: 2 % / Rmerge(I) obs: 0.3401 / Mean I/σ(I) obs: 3 / Num. unique obs: 691 / CC1/2: 0.598 / Rpim(I) all: 0.3089 / Rrim(I) all: 0.4368

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Processing

Software
NameVersionClassification
PHENIX1.19.2_4158refinement
XSCALEdata scaling
PDB_EXTRACT3.27data extraction
autoPROCdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: AlphaFold

Resolution: 2.95→50 Å / SU ML: 0.3 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 24.48 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2409 1141 4.94 %
Rwork0.2187 21941 -
obs0.2198 23082 78.48 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 427.3 Å2 / Biso mean: 66 Å2 / Biso min: 16.16 Å2
Refinement stepCycle: final / Resolution: 2.95→50 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4818 0 71 65 4954
Biso mean--106.37 41.79 -
Num. residues----633
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.95-3.070.3845320.358986025
3.07-3.240.3281720.2907131138
3.24-3.440.27361170.2764223965
3.44-3.70.27741810.2539341699
3.7-4.080.26251840.20783471100
4.08-4.670.18881740.16993495100
4.67-5.880.20212100.18533487100
5.88-500.26141710.2406366298
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.7893-0.71320.51963.8264-0.34153.2341-0.14230.16250.15960.63990.0843-0.3431-0.42330.19110.02650.32410.1284-0.06380.32840.06690.306711.6551-18.675418.5881
21.50240.2020.44934.1101-0.64052.08050.0276-0.297-0.11820.2347-0.03850.3046-0.8099-0.4749-0.01720.63520.1920.09030.59230.11440.40216.7823-48.287647.2148
32.28790.258-0.12835.17520.22953.07530.08760.1714-0.2663-0.19330.1330.36720.2897-0.197-0.23340.20310.0441-0.04740.40970.04480.2963.349-36.43488.5286
41.4988-0.0032-0.5882.2104-0.27821.42570.1827-0.04950.2497-0.04080.24080.6371-0.5982-1.0284-0.16460.43890.2449-0.02250.97920.25260.7018-5.8092-47.768536.1094
51.3621-1.1557-1.07993.11841.29083.81720.11540.14520.076-0.4164-0.2513-0.2006-0.08630.32270.1620.2390.0249-0.04060.41160.13990.32817.282-7.702-18.6723
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'H' and (resid 1 through 113 )H1 - 113
2X-RAY DIFFRACTION2chain 'H' and (resid 114 through 214 )H114 - 214
3X-RAY DIFFRACTION3chain 'L' and (resid 2 through 108 )L2 - 108
4X-RAY DIFFRACTION4chain 'L' and (resid 109 through 210 )L109 - 210
5X-RAY DIFFRACTION5chain 'H' and (resid 301 through 315 )H301 - 315
6X-RAY DIFFRACTION5chain 'L' and (resid 401 through 419 )L401 - 419
7X-RAY DIFFRACTION5chain 'R' and (resid 701 through 731 )R701 - 731

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