+Open data
-Basic information
Entry | Database: PDB / ID: 7sg6 | ||||||
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Title | Structure of PfCSP peptide 21 with antibody CIS43_Var10 | ||||||
Components |
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Keywords | IMMUNE SYSTEM / Antibody / Plasmodium falciparum | ||||||
Biological species | Homo sapiens (human) synthetic construct (others) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.55 Å | ||||||
Authors | Tripathi, P. / Kwong, P.D. | ||||||
Funding support | United States, 1items
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Citation | Journal: J Exp Med / Year: 2022 Title: Highly protective antimalarial antibodies via precision library generation and yeast display screening. Authors: Bailey B Banach / Prabhanshu Tripathi / Lais Da Silva Pereira / Jason Gorman / Thuy Duong Nguyen / Marlon Dillon / Ahmed S Fahad / Patience K Kiyuka / Bharat Madan / Jacy R Wolfe / Brian ...Authors: Bailey B Banach / Prabhanshu Tripathi / Lais Da Silva Pereira / Jason Gorman / Thuy Duong Nguyen / Marlon Dillon / Ahmed S Fahad / Patience K Kiyuka / Bharat Madan / Jacy R Wolfe / Brian Bonilla / Barbara Flynn / Joseph R Francica / Nicholas K Hurlburt / Neville K Kisalu / Tracy Liu / Li Ou / Reda Rawi / Arne Schön / Chen-Hsiang Shen / I-Ting Teng / Baoshan Zhang / Marie Pancera / Azza H Idris / Robert A Seder / Peter D Kwong / Brandon J DeKosky / Abstract: The monoclonal antibody CIS43 targets the Plasmodium falciparum circumsporozoite protein (PfCSP) and prevents malaria infection in humans for up to 9 mo following a single intravenous administration. ...The monoclonal antibody CIS43 targets the Plasmodium falciparum circumsporozoite protein (PfCSP) and prevents malaria infection in humans for up to 9 mo following a single intravenous administration. To enhance the potency and clinical utility of CIS43, we used iterative site-saturation mutagenesis and DNA shuffling to screen precise gene-variant yeast display libraries for improved PfCSP antigen recognition. We identified several mutations that improved recognition, predominately in framework regions, and combined these to produce a panel of antibody variants. The most improved antibody, CIS43_Var10, had three mutations and showed approximately sixfold enhanced protective potency in vivo compared to CIS43. Co-crystal and cryo-electron microscopy structures of CIS43_Var10 with the peptide epitope or with PfCSP, respectively, revealed functional roles for each of these mutations. The unbiased site-directed mutagenesis and screening pipeline described here represent a powerful approach to enhance protective potency and to enable broader clinical use of antimalarial antibodies. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7sg6.cif.gz | 108.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7sg6.ent.gz | 79.5 KB | Display | PDB format |
PDBx/mmJSON format | 7sg6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sg/7sg6 ftp://data.pdbj.org/pub/pdb/validation_reports/sg/7sg6 | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Antibody | Mass: 24281.320 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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#2: Antibody | Mass: 24160.670 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
#3: Protein/peptide | Mass: 1562.553 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
#4: Chemical | ChemComp-GOL / |
#5: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.08 Å3/Da / Density % sol: 40.91 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop Details: 15% ISOPROPANOL, 0.2M AMMONIUM CITRATE pH 3.5, 25% PEG 3,350 |
-Data collection
Diffraction | Mean temperature: 298 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Sep 29, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.55→44.96 Å / Num. obs: 58909 / % possible obs: 98.6 % / Redundancy: 3.5 % / CC1/2: 0.985 / Rmerge(I) obs: 0.132 / Net I/σ(I): 5.6 |
Reflection shell | Resolution: 1.55→1.6 Å / Rmerge(I) obs: 0.846 / Num. unique obs: 5896 / CC1/2: 0.56 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6B5M Resolution: 1.55→44.96 Å / SU ML: 0.16 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 21.87 / 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: 49.22 Å2 / Biso mean: 16.408 Å2 / Biso min: 5.77 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.55→44.96 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
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