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Yorodumi- PDB-7mxp: Cryo-EM structure of NTD-directed neutralizing antibody LP5 Fab i... -
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-Basic information
Entry | Database: PDB / ID: 7mxp | ||||||
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Title | Cryo-EM structure of NTD-directed neutralizing antibody LP5 Fab in complex with SARS-CoV-2 S2P spike | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Neturalsing antibody / Fusion protein / Spike glycoprotein / NRD / NTD-directed antibody / LP5 / Viral Protein / 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 / 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: 4.46 Å | ||||||
Authors | Reddem, E.R. / Casner, R.G. / Shapiro, L. | ||||||
Funding support | China, 1items
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Citation | Journal: AIChE J / Year: 2021 Title: Antibody screening at reduced pH enables preferential selection of potently neutralizing antibodies targeting SARS-CoV-2. Authors: Bharat Madan / Eswar R Reddem / Pengfei Wang / Ryan G Casner / Manoj S Nair / Yaoxing Huang / Ahmed S Fahad / Matheus Oliveira de Souza / Bailey B Banach / Sheila N López Acevedo / Xiaoli ...Authors: Bharat Madan / Eswar R Reddem / Pengfei Wang / Ryan G Casner / Manoj S Nair / Yaoxing Huang / Ahmed S Fahad / Matheus Oliveira de Souza / Bailey B Banach / Sheila N López Acevedo / Xiaoli Pan / Rajani Nimrania / I-Ting Teng / Fabiana Bahna / Tongqing Zhou / Baoshan Zhang / Michael T Yin / David D Ho / Peter D Kwong / Lawrence Shapiro / Brandon J DeKosky / Abstract: Antiviral monoclonal antibody (mAb) discovery enables the development of antibody-based antiviral therapeutics. Traditional antiviral mAb discovery relies on affinity between antibody and a viral ...Antiviral monoclonal antibody (mAb) discovery enables the development of antibody-based antiviral therapeutics. Traditional antiviral mAb discovery relies on affinity between antibody and a viral antigen to discover potent neutralizing antibodies, but these approaches are inefficient because many high affinity mAbs have no neutralizing activity. We sought to determine whether screening for anti-SARS-CoV-2 mAbs at reduced pH could provide more efficient neutralizing antibody discovery. We mined the antibody response of a convalescent COVID-19 patient at both physiological pH (7.4) and reduced pH (4.5), revealing that SARS-CoV-2 neutralizing antibodies were preferentially enriched in pH 4.5 yeast display sorts. Structural analysis revealed that a potent new antibody called LP5 targets the SARS-CoV-2 N-terminal domain supersite via a unique binding recognition mode. Our data combine with evidence from prior studies to support antibody screening at pH 4.5 to accelerate antiviral neutralizing antibody discovery. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7mxp.cif.gz | 700.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7mxp.ent.gz | 582.6 KB | Display | PDB format |
PDBx/mmJSON format | 7mxp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7mxp_validation.pdf.gz | 2.3 MB | Display | wwPDB validaton report |
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Full document | 7mxp_full_validation.pdf.gz | 2.3 MB | Display | |
Data in XML | 7mxp_validation.xml.gz | 108.6 KB | Display | |
Data in CIF | 7mxp_validation.cif.gz | 167.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mx/7mxp ftp://data.pdbj.org/pub/pdb/validation_reports/mx/7mxp | HTTPS FTP |
-Related structure data
Related structure data | 24075MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 1 types, 3 molecules ABC
#1: Protein | Mass: 142461.500 Da / Num. of mol.: 3 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 |
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-Antibody , 2 types, 6 molecules GIHJKL
#2: Antibody | Mass: 13263.756 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: 11445.481 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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-Sugars , 4 types, 35 molecules
#4: Polysaccharide | Type: oligosaccharide / Mass: 1463.349 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source #5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #7: Sugar | ChemComp-NAG / |
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-Details
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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Buffer solution | pH: 4.5 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
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: OTHER |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 42 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.46 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 96531 / Symmetry type: POINT | ||||||||||||||||||||||||
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