+Open data
-Basic information
Entry | Database: PDB / ID: 7ra8 | ||||||
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Title | SARS-CoV-2 S glycoprotein in complex with S2X259 Fab | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / Spike glycoprotein / Fab S2X259 / VIRAL PROTEIN / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / 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 / suppression by virus 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 / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / membrane fusion / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / 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 / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||
Authors | Veesler, D. / Tortorici, M.A. / Seattle Structural Genomics Center for Infectious Disease (SSGCID) | ||||||
Funding support | United States, 1items
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Citation | Journal: Nature / Year: 2021 Title: Broad sarbecovirus neutralization by a human monoclonal antibody. Authors: M Alejandra Tortorici / Nadine Czudnochowski / Tyler N Starr / Roberta Marzi / Alexandra C Walls / Fabrizia Zatta / John E Bowen / Stefano Jaconi / Julia Di Iulio / Zhaoqian Wang / Anna De ...Authors: M Alejandra Tortorici / Nadine Czudnochowski / Tyler N Starr / Roberta Marzi / Alexandra C Walls / Fabrizia Zatta / John E Bowen / Stefano Jaconi / Julia Di Iulio / Zhaoqian Wang / Anna De Marco / Samantha K Zepeda / Dora Pinto / Zhuoming Liu / Martina Beltramello / Istvan Bartha / Michael P Housley / Florian A Lempp / Laura E Rosen / Exequiel Dellota / Hannah Kaiser / Martin Montiel-Ruiz / Jiayi Zhou / Amin Addetia / Barbara Guarino / Katja Culap / Nicole Sprugasci / Christian Saliba / Eneida Vetti / Isabella Giacchetto-Sasselli / Chiara Silacci Fregni / Rana Abdelnabi / Shi-Yan Caroline Foo / Colin Havenar-Daughton / Michael A Schmid / Fabio Benigni / Elisabetta Cameroni / Johan Neyts / Amalio Telenti / Herbert W Virgin / Sean P J Whelan / Gyorgy Snell / Jesse D Bloom / Davide Corti / David Veesler / Matteo Samuele Pizzuto / Abstract: The recent emergence of SARS-CoV-2 variants of concern and the recurrent spillovers of coronaviruses into the human population highlight the need for broadly neutralizing antibodies that are not ...The recent emergence of SARS-CoV-2 variants of concern and the recurrent spillovers of coronaviruses into the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here we describe a human monoclonal antibody designated S2X259, which recognizes a highly conserved cryptic epitope of the receptor-binding domain and cross-reacts with spikes from all clades of sarbecovirus. S2X259 broadly neutralizes spike-mediated cell entry of SARS-CoV-2, including variants of concern (B.1.1.7, B.1.351, P.1, and B.1.427/B.1.429), as well as a wide spectrum of human and potentially zoonotic sarbecoviruses through inhibition of angiotensin-converting enzyme 2 (ACE2) binding to the receptor-binding domain. Furthermore, deep-mutational scanning and in vitro escape selection experiments demonstrate that S2X259 possesses an escape profile that is limited to a single substitution, G504D. We show that prophylactic and therapeutic administration of S2X259 protects Syrian hamsters (Mesocricetus auratus) against challenge with the prototypic SARS-CoV-2 and the B.1.351 variant of concern, which suggests that this monoclonal antibody is a promising candidate for the prevention and treatment of emergent variants and zoonotic infections. Our data reveal a key antigenic site that is targeted by broadly neutralizing antibodies and will guide the design of vaccines that are effective against all sarbecoviruses. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7ra8.cif.gz | 628.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7ra8.ent.gz | 499.4 KB | Display | PDB format |
PDBx/mmJSON format | 7ra8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7ra8_validation.pdf.gz | 3 MB | Display | wwPDB validaton report |
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Full document | 7ra8_full_validation.pdf.gz | 3 MB | Display | |
Data in XML | 7ra8_validation.xml.gz | 91.6 KB | Display | |
Data in CIF | 7ra8_validation.cif.gz | 143.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ra/7ra8 ftp://data.pdbj.org/pub/pdb/validation_reports/ra/7ra8 | HTTPS FTP |
-Related structure data
Related structure data | 24347MC 7ralC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 142427.438 Da / Num. of mol.: 3 Mutation: R682G, R683S, R685S, F817P, A892P, A899P, A942P, K986P, V987P Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #2: Antibody | Mass: 13755.396 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #3: Antibody | Mass: 11706.813 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #5: Sugar | ChemComp-NAG / Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Source (natural) |
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Source (recombinant) |
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Details of virus | Empty: YES / Enveloped: YES / Isolate: OTHER / Type: VIRUS-LIKE PARTICLE | ||||||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||||||
Specimen | Embedding applied: YES / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
EM embedding | Material: Tris buffer saline | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||
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Symmetry |
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3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 251102 / Symmetry type: POINT |