+Open data
-Basic information
Entry | Database: PDB / ID: 6okq | |||||||||
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Title | Crystal structure of the SF12 Fab | |||||||||
Components |
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Keywords | IMMUNE SYSTEM / HIV-1 broadly-neutralizing antibody / Fab structure / silent face / Envelope | |||||||||
Function / homology | Function and homology information immunoglobulin complex / adaptive immune response / extracellular region / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.2 Å | |||||||||
Authors | Barnes, C.O. / Bjorkman, P.J. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Immunity / Year: 2019 Title: Broad and Potent Neutralizing Antibodies Recognize the Silent Face of the HIV Envelope. Authors: Till Schoofs / Christopher O Barnes / Nina Suh-Toma / Jovana Golijanin / Philipp Schommers / Henning Gruell / Anthony P West / Franziska Bach / Yu Erica Lee / Lilian Nogueira / Ivelin S ...Authors: Till Schoofs / Christopher O Barnes / Nina Suh-Toma / Jovana Golijanin / Philipp Schommers / Henning Gruell / Anthony P West / Franziska Bach / Yu Erica Lee / Lilian Nogueira / Ivelin S Georgiev / Robert T Bailer / Julie Czartoski / John R Mascola / Michael S Seaman / M Juliana McElrath / Nicole A Doria-Rose / Florian Klein / Michel C Nussenzweig / Pamela J Bjorkman / Abstract: Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization ...Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization breadth from an HIV-infected donor. SF12 recognized a glycan-dominated epitope on Env's silent face and was potent against clade AE viruses, which are poorly covered by V3-glycan bNAbs. A 3.3Å cryo-EM structure of a SF12-Env trimer complex showed additional contacts to Env protein residues by SF12 compared with VRC-PG05, the only other known donor-derived silentface antibody, explaining SF12's increased neutralization breadth, potency, and resistance to Env mutation routes. Asymmetric binding of SF12 was associated with distinct N-glycan conformations across Env protomers, demonstrating intra-Env glycan heterogeneity. Administrating SF12 to HIV-1-infected humanized mice suppressed viremia and selected for viruses lacking the N448 glycan. Effective bNAbs can therefore be raised against HIV-1 Env's silent face, suggesting their potential for HIV-1 prevention, therapy, and vaccine development. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6okq.cif.gz | 257.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6okq.ent.gz | 208.8 KB | Display | PDB format |
PDBx/mmJSON format | 6okq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ok/6okq ftp://data.pdbj.org/pub/pdb/validation_reports/ok/6okq | HTTPS FTP |
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-Related structure data
Related structure data | 6okpC 1u6aS 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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2 |
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3 |
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Unit cell |
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-Components
#1: Antibody | Mass: 26155.338 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Plasmid: pTT5 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P0DOX5 #2: Antibody | Mass: 23108.842 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Plasmid: pTT5 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q8TCD0 |
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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: 7 Å3/Da / Density % sol: 82.43 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: 100 mM HEPES, pH 7.5, 1.8 M sodium formate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: May 19, 2018 |
Radiation | Monochromator: double crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 3.2→39.28 Å / Num. obs: 70865 / % possible obs: 99.6 % / Redundancy: 60.4 % / Biso Wilson estimate: 81.6 Å2 / Rmerge(I) obs: 0.216 / Net I/σ(I): 22.8 |
Reflection shell | Resolution: 3.2→3.26 Å / Redundancy: 56.8 % / Rmerge(I) obs: 2.55 / Mean I/σ(I) obs: 1.4 / Num. unique obs: 4473 / % possible all: 98.7 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 1U6A Resolution: 3.2→39.25 Å / SU ML: 0.46 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 40.91
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.2→39.25 Å
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Refine LS restraints |
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LS refinement shell |
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