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- PDB-7p40: P5C3 is a potent fab neutralizer -

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Basic information

Entry
Database: PDB / ID: 7p40
TitleP5C3 is a potent fab neutralizer
Components
  • Spike glycoproteinSpike protein
  • Variable Heavy Chain P5C3 (VH)
  • Variable Light Chain P5C3 (VL)
KeywordsVIRAL PROTEIN / spike / antibody
Function / homology
Function and homology information


endocytosis involved in viral entry into host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated virion attachment to host cell / membrane => GO:0016020 / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / host cell plasma membrane / virion 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 speciesSevere acute respiratory syndrome coronavirus 2
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å
Authorsperez, L.
CitationJournal: Cell Rep / Year: 2021
Title: A highly potent antibody effective against SARS-CoV-2 variants of concern.
Authors: Craig Fenwick / Priscilla Turelli / Laurent Perez / Céline Pellaton / Line Esteves-Leuenberger / Alex Farina / Jérémy Campos / Erica Lana / Flurin Fiscalini / Charlène Raclot / Florence ...Authors: Craig Fenwick / Priscilla Turelli / Laurent Perez / Céline Pellaton / Line Esteves-Leuenberger / Alex Farina / Jérémy Campos / Erica Lana / Flurin Fiscalini / Charlène Raclot / Florence Pojer / Kelvin Lau / Davide Demurtas / Marc Descatoire / Victor S Joo / Mathilde Foglierini / Alessandra Noto / Rana Abdelnabi / Caroline S Foo / Laura Vangeel / Johan Neyts / Wenjuan Du / Berend-Jan Bosch / Geertruida Veldman / Pieter Leyssen / Volker Thiel / Roger LeGrand / Yves Lévy / Didier Trono / Giuseppe Pantaleo /
Abstract: Control of the ongoing SARS-CoV-2 pandemic is endangered by the emergence of viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies, and reduced ...Control of the ongoing SARS-CoV-2 pandemic is endangered by the emergence of viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies, and reduced sensitivity to vaccine-induced immunity. Here, we screen B cells from COVID-19 donors and identify P5C3, a highly potent and broadly neutralizing monoclonal antibody with picomolar neutralizing activity against all SARS-CoV-2 variants of concern (VOCs) identified to date. Structural characterization of P5C3 Fab in complex with the spike demonstrates a neutralizing activity defined by a large buried surface area, highly overlapping with the receptor-binding domain (RBD) surface necessary for ACE2 interaction. We further demonstrate that P5C3 shows complete prophylactic protection in the SARS-CoV-2-infected hamster challenge model. These results indicate that P5C3 opens exciting perspectives either as a prophylactic agent in immunocompromised individuals with poor response to vaccination or as combination therapy in SARS-CoV-2-infected individuals.
History
DepositionJul 9, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 13, 2021Provider: repository / Type: Initial release
Revision 1.1Oct 27, 2021Group: Data collection / Database references / Category: citation / em_admin / pdbx_database_proc / Item: _citation.journal_volume / _em_admin.last_update
SupersessionApr 12, 2023ID: 7NY5
Revision 1.2Apr 12, 2023Group: Advisory / Refinement description
Category: pdbx_database_PDB_obs_spr / pdbx_initial_refinement_model

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Structure visualization

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  • Deposited structure unit
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  • EMDB-13190
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Structure viewerMolecule:
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Assembly

Deposited unit
A: Spike glycoprotein
B: Variable Light Chain P5C3 (VL)
C: Variable Heavy Chain P5C3 (VH)
D: Variable Light Chain P5C3 (VL)
E: Spike glycoprotein
F: Variable Heavy Chain P5C3 (VH)
G: Spike glycoprotein
H: Variable Light Chain P5C3 (VL)
I: Variable Heavy Chain P5C3 (VH)


Theoretical massNumber of molelcules
Total (without water)564,9369
Polymers564,9369
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: microscopy
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area29180 Å2
ΔGint-175 kcal/mol
Surface area162680 Å2

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Components

#1: Protein Spike glycoprotein / Spike protein / S glycoprotein / E2 / Peplomer protein


Mass: 141560.859 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Details: ...Details: MGILPSPGMPALLSLVSLLSVLLMGCVAETGTQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPSGAGSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVA KNLNESLIDLQELGKYEQYIKGSGRENLYFQGGGGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGHHHHHHHH
Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2
Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: A0A6N1BWN9
#2: Antibody Variable Light Chain P5C3 (VL)


Mass: 23388.875 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)
#3: Antibody Variable Heavy Chain P5C3 (VH)


Mass: 23362.133 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1Severe acute respiratory syndrome coronavirus 2SARS-CoV-2COMPLEXall0RECOMBINANT
2Spike glycoproteinSpike proteinCOMPLEX#11RECOMBINANT
3FabFragment antigen-bindingCOMPLEX#2-#31RECOMBINANT
Molecular weightUnits: KILODALTONS/NANOMETER / Experimental value: YES
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
22Severe acute respiratory syndrome coronavirus 22697049
33Homo sapiens (human)9606
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
22Cricetulus griseus (Chinese hamster)10029
33Cricetulus griseus (Chinese hamster)10029
Details of virusEmpty: NO / Enveloped: YES / Isolate: OTHER / Type: VIRUS-LIKE PARTICLE
Buffer solutionpH: 7.3
Buffer componentConc.: 150 mM / Name: PBS / Formula: PBS
SpecimenConc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid type: Quantifoil R2/2
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 %

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 10500 X / Calibrated magnification: 10500 X / Calibrated defocus min: 800 nm / Calibrated defocus max: 2500 nm / Cs: 2.27 mm / Alignment procedure: BASIC
Specimen holderCryogen: HELIUM / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 38 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 12303
EM imaging opticsEnergyfilter name: GIF Quantum LS / Phase plate: OTHER

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Processing

EM software
IDNameVersionCategory
2SerialEMimage acquisition
4CTFFINDCTF correction
7Cootmodel fitting
9CTFFINDinitial Euler assignment
10cryoSPARC3.0.1final Euler assignment
11cryoSPARC3.0.1classification
12Coot3D reconstruction
13PHENIX3D reconstruction
14PHENIXmodel refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 21000000
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 585005 / Algorithm: FOURIER SPACE / Num. of class averages: 1 / Symmetry type: POINT
Atomic model buildingB value: 120 / Protocol: OTHER / Space: REAL / Target criteria: 0.8
Atomic model buildingPDB-ID: 7K4N

7k4n

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