[English] 日本語
Yorodumi- PDB-6vi0: Cryo-EM structure of VRC01.23 in complex with HIV-1 Env BG505 DS.SOSIP -
+Open data
-Basic information
Entry | Database: PDB / ID: 6vi0 | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of VRC01.23 in complex with HIV-1 Env BG505 DS.SOSIP | ||||||
Components |
| ||||||
Keywords | IMMUNE SYSTEM / CD4 / HIV-1 / SOSIP / Vaccine | ||||||
Function / homology | Function and homology information positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope ...positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / structural molecule activity / virion membrane / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | Human immunodeficiency virus 1 Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.43 Å | ||||||
Authors | Gorman, J. / Kwong, P.D. | ||||||
Funding support | United States, 1items
| ||||||
Citation | Journal: MAbs / Year: 2021 Title: A matrix of structure-based designs yields improved VRC01-class antibodies for HIV-1 therapy and prevention. Authors: Young D Kwon / Mangaiarkarasi Asokan / Jason Gorman / Baoshan Zhang / Qingbo Liu / Mark K Louder / Bob C Lin / Krisha McKee / Amarendra Pegu / Raffaello Verardi / Eun Sung Yang / Vrc ...Authors: Young D Kwon / Mangaiarkarasi Asokan / Jason Gorman / Baoshan Zhang / Qingbo Liu / Mark K Louder / Bob C Lin / Krisha McKee / Amarendra Pegu / Raffaello Verardi / Eun Sung Yang / Vrc Production Program / Kevin Carlton / Nicole A Doria-Rose / Paolo Lusso / John R Mascola / Peter D Kwong / Abstract: Passive transfer of broadly neutralizing antibodies is showing promise in the treatment and prevention of HIV-1. One class of antibodies, the VRC01 class, appears especially promising. To improve ...Passive transfer of broadly neutralizing antibodies is showing promise in the treatment and prevention of HIV-1. One class of antibodies, the VRC01 class, appears especially promising. To improve VRC01-class antibodies, we combined structure-based design with a matrix-based approach to generate VRC01-class variants that filled an interfacial cavity, used diverse third-complementarity-determining regions, reduced potential steric clashes, or exploited extended contacts to a neighboring protomer within the envelope trimer. On a 208-strain panel, variant VRC01.23LS neutralized 90% of the panel at a geometric mean IC less than 1 μg/ml, and in transgenic mice with human neonatal-Fc receptor, the serum half-life of VRC01.23LS was indistinguishable from that of the parent VRC01LS, which has a half-life of 71 d in humans. A cryo-electron microscopy structure of VRC01.23 Fab in complex with BG505 DS-SOSIP.664 Env trimer determined at 3.4-Å resolution confirmed the structural basis for its ~10-fold improved potency relative to VRC01. Another variant, VRC07-523-F54-LS.v3, neutralized 95% of the 208-isolated panel at a geometric mean IC of less than 1 μg/ml, with a half-life comparable to that of the parental VRC07-523LS. Our matrix-based structural approach thus enables the engineering of VRC01 variants for HIV-1 therapy and prevention with improved potency, breadth, and pharmacokinetics. | ||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6vi0.cif.gz | 476 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6vi0.ent.gz | 399.5 KB | Display | PDB format |
PDBx/mmJSON format | 6vi0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6vi0_validation.pdf.gz | 2.8 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 6vi0_full_validation.pdf.gz | 2.9 MB | Display | |
Data in XML | 6vi0_validation.xml.gz | 80.6 KB | Display | |
Data in CIF | 6vi0_validation.cif.gz | 117.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vi/6vi0 ftp://data.pdbj.org/pub/pdb/validation_reports/vi/6vi0 | HTTPS FTP |
-Related structure data
Related structure data | 21208MC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Protein , 3 types, 9 molecules BAFGCILDJ
#1: Protein | Mass: 17146.482 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q2N0S6 #2: Protein | Mass: 54086.324 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q2N0S6 #3: Protein | Mass: 22761.166 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) |
---|
-Antibody , 1 types, 3 molecules HEK
#4: Antibody | Mass: 25109.400 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
---|
-Sugars , 7 types, 60 molecules
#5: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #6: Polysaccharide | Source method: isolated from a genetically manipulated source #7: Polysaccharide | Source method: isolated from a genetically manipulated source #8: Polysaccharide | Source method: isolated from a genetically manipulated source #9: Polysaccharide | Source method: isolated from a genetically manipulated source #10: Polysaccharide | Source method: isolated from a genetically manipulated source #11: Sugar | ChemComp-NAG / |
---|
-Details
Has ligand of interest | N |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
| ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Experimental value: NO | ||||||||||||||||||
Source (natural) | Organism: Human immunodeficiency virus 1 | ||||||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||
Buffer component | Formula: PBS | ||||||||||||||||||
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 90 % / Chamber temperature: 293 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / C2 aperture diameter: 70 µm |
Image recording | Average exposure time: 10 sec. / Electron dose: 70.41 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 1882 |
-Processing
Software | Name: PHENIX / Version: 1.16_3549: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software |
| ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 153590 | ||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.43 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 55046 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 6NNF | ||||||||||||||||||||||||
Refine LS restraints |
|