[English] 日本語
Yorodumi- PDB-6o3d: Crystal structure of the unbound Fab fragment of the human HIV-1 ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6o3d | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal structure of the unbound Fab fragment of the human HIV-1 neutralizing antibody PGZL1. | ||||||
Components |
| ||||||
Keywords | IMMUNE SYSTEM / PGZL1 ANTI HIV-1 / GP41 MPER / MEMBRANE LIPIDS / BROADLY NEUTRALISING HIV-1 ANTIBODY | ||||||
Function / homology | Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta Function and homology information | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.402 Å | ||||||
Authors | Irimia, A. / Wilson, I.A. | ||||||
Funding support | United States, 1items
| ||||||
Citation | Journal: Nat Commun / Year: 2019 Title: An MPER antibody neutralizes HIV-1 using germline features shared among donors. Authors: Lei Zhang / Adriana Irimia / Lingling He / Elise Landais / Kimmo Rantalainen / Daniel P Leaman / Thomas Vollbrecht / Armando Stano / Daniel I Sands / Arthur S Kim / / Pascal Poignard / ...Authors: Lei Zhang / Adriana Irimia / Lingling He / Elise Landais / Kimmo Rantalainen / Daniel P Leaman / Thomas Vollbrecht / Armando Stano / Daniel I Sands / Arthur S Kim / / Pascal Poignard / Dennis R Burton / Ben Murrell / Andrew B Ward / Jiang Zhu / Ian A Wilson / Michael B Zwick / Abstract: The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic ...The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic CDRH3s, lack activity as inferred germline precursors, are often from the minor IgG3 subclass, and some are polyreactive, such as 4E10. Here we describe an MPER broadly neutralizing antibody from the major IgG1 subclass, PGZL1, which shares germline V/D-region genes with 4E10, has a shorter CDRH3, and is less polyreactive. A recombinant sublineage variant pan-neutralizes a 130-isolate panel at 1.4 μg/ml (IC). Notably, a germline revertant with mature CDR3s neutralizes 12% of viruses and still binds MPER after DJ reversion. Crystal structures of lipid-bound PGZL1 variants and cryo-EM reconstruction of an Env-PGZL1 complex reveal how these antibodies recognize MPER and viral membrane. Discovery of common genetic and structural elements among MPER antibodies from different patients suggests that such antibodies could be elicited using carefully designed immunogens. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 6o3d.cif.gz | 209.8 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6o3d.ent.gz | 166.4 KB | Display | PDB format |
PDBx/mmJSON format | 6o3d.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/o3/6o3d ftp://data.pdbj.org/pub/pdb/validation_reports/o3/6o3d | HTTPS FTP |
---|
-Related structure data
Related structure data | 0620C 6o3gC 6o3jC 6o3kC 6o3lC 6o3uC 6o41C 6o42C 2fx7S C: citing same article (ref.) S: Starting model for refinement |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 |
| |||||||||||||||
Unit cell |
| |||||||||||||||
Components on special symmetry positions |
|
-Components
#1: Antibody | Mass: 23300.748 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Expi 293F / Production host: Homo sapiens (human) | ||||
---|---|---|---|---|---|
#2: Antibody | Mass: 23913.920 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Expi 293F / Production host: Homo sapiens (human) | ||||
#3: Chemical | ChemComp-GOL / #4: Chemical | ChemComp-SO4 / | #5: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.54 Å3/Da / Density % sol: 51.1 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 4.6 Details: Reservoir: 20% PEG 4000, 20% glycerol, 0.08 M sodium acetate pH 4.6, 0.16 M ammonium sulfate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL9-2 / Wavelength: 0.97946 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 12, 2017 / Details: NULL |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97946 Å / Relative weight: 1 |
Reflection | Resolution: 1.4→37.0477 Å / Num. obs: 89730 / % possible obs: 95.4 % / Redundancy: 3.3 % / Biso Wilson estimate: 17 Å2 / Rpim(I) all: 0.052 / Rsym value: 0.082 / Net I/σ(I): 7.8 |
Reflection shell | Resolution: 1.4→1.42 Å / Redundancy: 2.7 % / Mean I/σ(I) obs: 1.4 / Num. unique obs: 3906 / Rpim(I) all: 0.609 / Rsym value: 0.891 / % possible all: 83.2 |
-Processing
Software |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2fx7 Resolution: 1.402→37.035 Å / SU ML: 0.16 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 19
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 24 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.402→37.035 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
|