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Yorodumi- PDB-8ekf: X-ray crystal structure of 311R Fab in complex with the PfCSP pep... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8ekf | ||||||
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Title | X-ray crystal structure of 311R Fab in complex with the PfCSP peptide NPNA-3 | ||||||
Components |
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Keywords | IMMUNE SYSTEM / Antibody / Antigen / Malaria | ||||||
Biological species | Homo sapiens (human) Plasmodium falciparum 3D7 (eukaryote) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å | ||||||
Authors | Moskovitz, R. / Wilson, I.A. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Commun / Year: 2023 Title: Affinity-matured homotypic interactions induce spectrum of PfCSP structures that influence protection from malaria infection. Authors: Gregory M Martin / Jonathan L Torres / Tossapol Pholcharee / David Oyen / Yevel Flores-Garcia / Grace Gibson / Re'em Moskovitz / Nathan Beutler / Diana D Jung / Jeffrey Copps / Wen-Hsin Lee ...Authors: Gregory M Martin / Jonathan L Torres / Tossapol Pholcharee / David Oyen / Yevel Flores-Garcia / Grace Gibson / Re'em Moskovitz / Nathan Beutler / Diana D Jung / Jeffrey Copps / Wen-Hsin Lee / Gonzalo Gonzalez-Paez / Daniel Emerling / Randall S MacGill / Emily Locke / C Richter King / Fidel Zavala / Ian A Wilson / Andrew B Ward / Abstract: The generation of high-quality antibody responses to Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP), the primary surface antigen of Pf sporozoites, is paramount to the development of an ...The generation of high-quality antibody responses to Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP), the primary surface antigen of Pf sporozoites, is paramount to the development of an effective malaria vaccine. Here we present an in-depth structural and functional analysis of a panel of potent antibodies encoded by the immunoglobulin heavy chain variable (IGHV) gene IGHV3-33, which is among the most prevalent and potent antibody families induced in the anti-PfCSP immune response and targets the Asn-Ala-Asn-Pro (NANP) repeat region. Cryo-electron microscopy (cryo-EM) reveals a remarkable spectrum of helical antibody-PfCSP structures stabilized by homotypic interactions between tightly packed fragments antigen binding (Fabs), many of which correlate with somatic hypermutation. We demonstrate a key role of these mutated homotypic contacts for high avidity binding to PfCSP and in protection from Pf malaria infection. Together, these data emphasize the importance of anti-homotypic affinity maturation in the frequent selection of IGHV3-33 antibodies and highlight key features underlying the potent protection of this antibody family. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ekf.cif.gz | 106.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ekf.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8ekf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ekf_validation.pdf.gz | 438.4 KB | Display | wwPDB validaton report |
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Full document | 8ekf_full_validation.pdf.gz | 440.1 KB | Display | |
Data in XML | 8ekf_validation.xml.gz | 18.5 KB | Display | |
Data in CIF | 8ekf_validation.cif.gz | 26.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ek/8ekf ftp://data.pdbj.org/pub/pdb/validation_reports/ek/8ekf | HTTPS FTP |
-Related structure data
Related structure data | 8dytC 8dywC 8dyxC 8dyyC 8dz3C 8dz4C 8dz5C 6axkS S: Starting model for refinement C: citing same article (ref.) |
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-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Antibody | Mass: 23927.830 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: 22839.268 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: 1207.210 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Plasmodium falciparum 3D7 (eukaryote) |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.85 Å3/Da / Density % sol: 56.86 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / Details: 0.04 M KH2PO4, 20% Glycerol, and 16% PEG3000 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL12-1 / Wavelength: 0.979 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: May 24, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.979 Å / Relative weight: 1 |
Reflection | Resolution: 1.9→44.27 Å / Num. obs: 44216 / % possible obs: 99.8 % / Redundancy: 3.3 % / CC1/2: 0.99 / Rmerge(I) obs: 0.055 / Net I/σ(I): 17.2 |
Reflection shell | Resolution: 1.9→1.94 Å / Redundancy: 2.3 % / Num. unique obs: 4800 / CC1/2: 0.96 / % possible all: 97.6 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6AXK Resolution: 1.9→44.27 Å / Cor.coef. Fo:Fc: 0.964 / Cor.coef. Fo:Fc free: 0.95 / SU B: 3.092 / SU ML: 0.087 / Cross valid method: FREE R-VALUE / ESU R: 0.126 / ESU R Free: 0.124 Details: Hydrogens have been added in their riding positions
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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 BULK SOLVENT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 37.602 Å2
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Refinement step | Cycle: LAST / Resolution: 1.9→44.27 Å
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Refine LS restraints |
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LS refinement shell |
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