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Yorodumi- PDB-7tp4: Crystal structure of SARS-CoV-2 receptor binding domain in comple... -
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-Basic information
Entry | Database: PDB / ID: 7tp4 | ||||||||||||
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Title | Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibody K398.22 | ||||||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / antibody / neutralizing antibody / Fab / COVID-19 / coronavirus / receptor-binding domain / RBD / 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 / 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 / receptor-mediated endocytosis of virus by host cell / membrane fusion / 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 Macaca mulatta (Rhesus monkey) | ||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.95 Å | ||||||||||||
Authors | Yuan, M. / Zhu, X. / Wilson, I.A. | ||||||||||||
Funding support | United States, 3items
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Citation | Journal: Sci Transl Med / Year: 2022 Title: Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques. Authors: Wan-Ting He / Meng Yuan / Sean Callaghan / Rami Musharrafieh / Ge Song / Murillo Silva / Nathan Beutler / Wen-Hsin Lee / Peter Yong / Jonathan L Torres / Mariane Melo / Panpan Zhou / Fangzhu ...Authors: Wan-Ting He / Meng Yuan / Sean Callaghan / Rami Musharrafieh / Ge Song / Murillo Silva / Nathan Beutler / Wen-Hsin Lee / Peter Yong / Jonathan L Torres / Mariane Melo / Panpan Zhou / Fangzhu Zhao / Xueyong Zhu / Linghang Peng / Deli Huang / Fabio Anzanello / James Ricketts / Mara Parren / Elijah Garcia / Melissa Ferguson / William Rinaldi / Stephen A Rawlings / David Nemazee / Davey M Smith / Bryan Briney / Yana Safonova / Thomas F Rogers / Jennifer M Dan / Zeli Zhang / Daniela Weiskopf / Alessandro Sette / Shane Crotty / Darrell J Irvine / Andrew B Ward / Ian A Wilson / Dennis R Burton / Raiees Andrabi / Abstract: To prepare for future coronavirus (CoV) pandemics, it is desirable to generate vaccines capable of eliciting broadly neutralizing antibody responses to CoVs. Here, we show that immunization of ...To prepare for future coronavirus (CoV) pandemics, it is desirable to generate vaccines capable of eliciting broadly neutralizing antibody responses to CoVs. Here, we show that immunization of macaques with SARS-CoV-2 spike (S) protein with a two-shot protocol generated potent serum receptor binding domain cross-neutralizing antibody responses to both SARS-CoV-2 and SARS-CoV-1. Furthermore, responses were equally effective against most SARS-CoV-2 variants of concern (VOCs) and some were highly effective against Omicron. This result contrasts with human infection or many two-shot vaccination protocols where responses were typically more SARS-CoV-2 specific and where VOCs were less well neutralized. Structural studies showed that cloned macaque neutralizing antibodies, particularly using a given heavy chain germline gene, recognized a relatively conserved region proximal to the angiotensin converting enzyme 2 receptor binding site (RBS), whereas many frequently elicited human neutralizing antibodies targeted more variable epitopes overlapping the RBS. B cell repertoire differences between humans and macaques appeared to influence the vaccine response. The macaque neutralizing antibodies identified a pan-SARS-related virus epitope region less well targeted by human antibodies that could be exploited in rational vaccine design. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7tp4.cif.gz | 145.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7tp4.ent.gz | 108.8 KB | Display | PDB format |
PDBx/mmJSON format | 7tp4.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7tp4_validation.pdf.gz | 1008.1 KB | Display | wwPDB validaton report |
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Full document | 7tp4_full_validation.pdf.gz | 1016.1 KB | Display | |
Data in XML | 7tp4_validation.xml.gz | 27.2 KB | Display | |
Data in CIF | 7tp4_validation.cif.gz | 39.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tp/7tp4 ftp://data.pdbj.org/pub/pdb/validation_reports/tp/7tp4 | HTTPS FTP |
-Related structure data
Related structure data | 7tp3C 6w41S S: Starting model for refinement 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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Unit cell |
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Components on special symmetry positions |
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-Components
-Antibody , 2 types, 2 molecules HL
#2: Antibody | Mass: 24160.125 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Macaca mulatta (Rhesus monkey) / Production host: Homo sapiens (human) |
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#3: Antibody | Mass: 22520.834 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Macaca mulatta (Rhesus monkey) / Production host: Homo sapiens (human) |
-Protein / Sugars , 2 types, 2 molecules Z
#1: Protein | Mass: 23104.867 Da / Num. of mol.: 1 / 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 |
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#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 Source method: isolated from a genetically manipulated source |
-Non-polymers , 2 types, 306 molecules
#5: Chemical | ChemComp-EDO / |
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#6: Water | ChemComp-HOH / |
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.99 Å3/Da / Density % sol: 58.83 % |
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Crystal grow | Temperature: 293.15 K / Method: vapor diffusion, sitting drop / Details: 0.2 M ammonium formate and 20% (w/v) PEG 3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 0.9793 Å | ||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Mar 3, 2021 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9793 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 1.74→47.19 Å / Num. obs: 89537 / % possible obs: 99.8 % / Redundancy: 12.1 % / CC1/2: 0.999 / Rmerge(I) obs: 0.09 / Rpim(I) all: 0.026 / Rrim(I) all: 0.094 / Net I/σ(I): 12.1 / Num. measured all: 1085173 / Scaling rejects: 21 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6W41 Resolution: 1.95→46.212 Å / SU ML: 0.24 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 30.98 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 104.64 Å2 / Biso mean: 53.2815 Å2 / Biso min: 30 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.95→46.212 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
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