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 Yorodumi
Yorodumi- PDB-7m7w: Antibodies to the SARS-CoV-2 receptor-binding domain that maximiz... -
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Open data
- Basic information
Basic information
| Entry | Database: PDB / ID: 7m7w | ||||||
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| Title | Antibodies to the SARS-CoV-2 receptor-binding domain that maximize breadth and resistance to viral escape | ||||||
|  Components | 
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|  Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / COVID-19 / SARS-CoV-2 / neutralizing monoclonal antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
| Function / homology |  Function and homology information symbiont-mediated disruption of host tissue / Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / viral translation / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion ...symbiont-mediated disruption of host tissue / Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / viral translation / 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 / symbiont entry into host cell / 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 |  Homo sapiens (human)   Severe acute respiratory syndrome coronavirus 2 | ||||||
| Method |  X-RAY DIFFRACTION /  SYNCHROTRON /  MOLECULAR REPLACEMENT / Resolution: 2.65 Å | ||||||
|  Authors | Snell, G. / Czudnochowski, N. / Croll, T.I. / Nix, J.C. / Corti, D. / Cameroni, E. / Pinto, D. / Beltramello, M. | ||||||
|  Citation |  Journal: Nature / Year: 2021 Title: SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape. Authors: Tyler N Starr / Nadine Czudnochowski / Zhuoming Liu / Fabrizia Zatta / Young-Jun Park / Amin Addetia / Dora Pinto / Martina Beltramello / Patrick Hernandez / Allison J Greaney / Roberta ...Authors: Tyler N Starr / Nadine Czudnochowski / Zhuoming Liu / Fabrizia Zatta / Young-Jun Park / Amin Addetia / Dora Pinto / Martina Beltramello / Patrick Hernandez / Allison J Greaney / Roberta Marzi / William G Glass / Ivy Zhang / Adam S Dingens / John E Bowen / M Alejandra Tortorici / Alexandra C Walls / Jason A Wojcechowskyj / Anna De Marco / Laura E Rosen / Jiayi Zhou / Martin Montiel-Ruiz / Hannah Kaiser / Josh R Dillen / Heather Tucker / Jessica Bassi / Chiara Silacci-Fregni / Michael P Housley / Julia di Iulio / Gloria Lombardo / Maria Agostini / Nicole Sprugasci / Katja Culap / Stefano Jaconi / Marcel Meury / Exequiel Dellota / Rana Abdelnabi / Shi-Yan Caroline Foo / Elisabetta Cameroni / Spencer Stumpf / Tristan I Croll / Jay C Nix / Colin Havenar-Daughton / Luca Piccoli / Fabio Benigni / Johan Neyts / Amalio Telenti / Florian A Lempp / Matteo S Pizzuto / John D Chodera / Christy M Hebner / Herbert W Virgin / Sean P J Whelan / David Veesler / Davide Corti / Jesse D Bloom / Gyorgy Snell /        Abstract: An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape, have activity against diverse sarbecoviruses, and be highly protective through viral neutralization and effector functions. ...An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape, have activity against diverse sarbecoviruses, and be highly protective through viral neutralization and effector functions. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E12) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics. #1: Journal: Biorxiv / Year: 2021 Title: Antibodies to the SARS-CoV-2 receptor-binding domain that maximize breadth and resistance to viral escape. Authors: Starr, T.N. / Czudnochowski, N. / Zatta, F. / Park, Y.J. / Liu, Z. / Addetia, A. / Pinto, D. / Beltramello, M. / Hernandez, P. / Greaney, A.J. / Marzi, R. / Glass, W.G. / Zhang, I. / ...Authors: Starr, T.N. / Czudnochowski, N. / Zatta, F. / Park, Y.J. / Liu, Z. / Addetia, A. / Pinto, D. / Beltramello, M. / Hernandez, P. / Greaney, A.J. / Marzi, R. / Glass, W.G. / Zhang, I. / Dingens, A.S. / Bowen, J.E. / Wojcechowskyj, J.A. / De Marco, A. / Rosen, L.E. / Zhou, J. / Montiel-Ruiz, M. / Kaiser, H. / Tucker, H. / Housley, M.P. / di Iulio, J. / Lombardo, G. / Agostini, M. / Sprugasci, N. / Culap, K. / Jaconi, S. / Meury, M. / Dellota, E. / Cameroni, E. / Croll, T.I. / Nix, J.C. / Havenar-Daughton, C. / Telenti, A. / Lempp, F.A. / Pizzuto, M.S. / Chodera, J.D. / Hebner, C.M. / Whelan, S.P.J. / Virgin, H.W. / Veesler, D. / Corti, D. / Bloom, J.D. / Snell, G. | ||||||
| History | 
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- Structure visualization
Structure visualization
| Structure viewer | Molecule:  Molmil  Jmol/JSmol | 
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- Downloads & links
Downloads & links
- Download
Download
| PDBx/mmCIF format |  7m7w.cif.gz | 820 KB | Display |  PDBx/mmCIF format | 
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| PDB format |  pdb7m7w.ent.gz | 681.3 KB | Display |  PDB format | 
| PDBx/mmJSON format |  7m7w.json.gz | Tree view |  PDBx/mmJSON format | |
| Others |  Other downloads | 
-Validation report
| Summary document |  7m7w_validation.pdf.gz | 515.9 KB | Display |  wwPDB validaton report | 
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| Full document |  7m7w_full_validation.pdf.gz | 530.5 KB | Display | |
| Data in XML |  7m7w_validation.xml.gz | 69.6 KB | Display | |
| Data in CIF |  7m7w_validation.cif.gz | 96.4 KB | Display | |
| Arichive directory |  https://data.pdbj.org/pub/pdb/validation_reports/m7/7m7w  ftp://data.pdbj.org/pub/pdb/validation_reports/m7/7m7w | HTTPS FTP | 
-Related structure data
| Related structure data |  7r6wC  7r6xC  7r7nC  7jx3S S: Starting model for refinement C: citing same article ( | 
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| Similar structure data | 
- Links
Links
- Assembly
Assembly
| Deposited unit |  
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| 2 |  
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| Unit cell | 
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- Components
Components
-Antibody , 4 types, 8 molecules BLAHDFCE       
| #1: Antibody | Mass: 22993.350 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.)  Homo sapiens (human) / Production host:   Cricetulus griseus (Chinese hamster) #2: Antibody | Mass: 24351.354 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.)  Homo sapiens (human) / Production host:   Cricetulus griseus (Chinese hamster) #3: Antibody | Mass: 22935.219 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.)  Homo sapiens (human) / Cell line (production host): HEK293 suspension / Production host:  Homo sapiens (human) #4: Antibody | Mass: 24174.143 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.)  Homo sapiens (human) / Cell line (production host): HEK293 suspension / Production host:  Homo sapiens (human) | 
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-Protein / Sugars / Non-polymers , 3 types, 99 molecules SR

 


| #5: Protein | Mass: 24442.332 Da / Num. of mol.: 2 / Fragment: receptor binding domain (UNP residues 328-531) 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 #6: Sugar | #7: Water | ChemComp-HOH / |  | 
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-Details
| Has ligand of interest | N | 
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| Has protein modification | Y | 
-Experimental details
-Experiment
| Experiment | Method:  X-RAY DIFFRACTION / Number of used crystals: 1 | 
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- Sample preparation
Sample preparation
| Crystal | Density Matthews: 2.95 Å3/Da / Density % sol: 58.36 % | 
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| Crystal grow | Temperature: 293.15 K / Method: vapor diffusion, sitting drop Details: 30% Precipitant Mix 2 (Molecular Dimensions; ethylene glycol, PEG8000), 0.1 M Buffer System 3, pH 8.5 (Molecular Dimensions; Tris (base)/BICINE), 0.12 M Monosaccharides Mix (Molecular ...Details: 30% Precipitant Mix 2 (Molecular Dimensions; ethylene glycol, PEG8000), 0.1 M Buffer System 3, pH 8.5 (Molecular Dimensions; Tris (base)/BICINE), 0.12 M Monosaccharides Mix (Molecular Dimensions), 0.02 M sodium chloride, 0.01 M MES, pH 6, 3% v/v Jeffamine ED-2003 | 
-Data collection
| Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | |||||||||||||||||||||||||||
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| Diffraction source | Source:  SYNCHROTRON / Site:  SSRL  / Beamline: BL9-2 / Wavelength: 0.97946 Å | |||||||||||||||||||||||||||
| Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 21, 2021 | |||||||||||||||||||||||||||
| Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||
| Radiation wavelength | Wavelength: 0.97946 Å / Relative weight: 1 | |||||||||||||||||||||||||||
| Reflection | Resolution: 2.65→63.94 Å / Num. obs: 77307 / % possible obs: 98.6 % / Redundancy: 6.9 % / CC1/2: 0.997 / Rmerge(I) obs: 0.149 / Rpim(I) all: 0.06 / Rrim(I) all: 0.161 / Net I/σ(I): 10.9 / Num. measured all: 533127 | |||||||||||||||||||||||||||
| Reflection shell | Diffraction-ID: 1 / % possible all: 98.3 
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- Processing
Processing
| Software | 
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| Refinement | Method to determine structure:  MOLECULAR REPLACEMENT Starting model: PDB entry 7JX3, homology models of S2X259 Fab and S2H97 Fab Resolution: 2.65→50.01 Å / Cor.coef. Fo:Fc: 0.941 / Cor.coef. Fo:Fc free: 0.908 / SU B: 39.291 / SU ML: 0.347 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.855 / ESU R Free: 0.347 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: U VALUES : WITH TLS ADDED 
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| Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Displacement parameters | Biso  max: 176.37 Å2 / Biso  mean: 75.747 Å2 / Biso  min: 30 Å2 
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| Refinement step | Cycle: final / Resolution: 2.65→50.01 Å 
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| Refine LS restraints | 
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| LS refinement shell | Resolution: 2.65→2.719 Å / Rfactor Rfree error: 0  / Total num. of bins used: 20 
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| Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION 
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| Refinement TLS group | 
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