+Open data
-Basic information
Entry | Database: PDB / ID: 7ugm | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Crystal Structure of BG24-iGL CDR3mat Fab | |||||||||
Components |
| |||||||||
Keywords | IMMUNE SYSTEM / Fab / IgG / BG24 / anti-HIV antibody / bNAb | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.4 Å | |||||||||
Authors | Dam, K.A. / Barnes, C.O. / Bjorkman, P.J. | |||||||||
Funding support | United States, 2items
| |||||||||
Citation | Journal: Nat Commun / Year: 2022 Title: HIV-1 CD4-binding site germline antibody-Env structures inform vaccine design. Authors: Kim-Marie A Dam / Christopher O Barnes / Harry B Gristick / Till Schoofs / Priyanthi N P Gnanapragasam / Michel C Nussenzweig / Pamela J Bjorkman / Abstract: BG24, a VRC01-class broadly neutralizing antibody (bNAb) against HIV-1 Env with relatively few somatic hypermutations (SHMs), represents a promising target for vaccine strategies to elicit CD4- ...BG24, a VRC01-class broadly neutralizing antibody (bNAb) against HIV-1 Env with relatively few somatic hypermutations (SHMs), represents a promising target for vaccine strategies to elicit CD4-binding site (CD4bs) bNAbs. To understand how SHMs correlate with BG24 neutralization of HIV-1, we report 4.1 Å and 3.4 Å single-particle cryo-EM structures of two inferred germline (iGL) BG24 precursors complexed with engineered Env-based immunogens lacking CD4bs N-glycans. Structures reveal critical Env contacts by BG24 and identify antibody light chain structural features that impede Env recognition. In addition, biochemical data and cryo-EM structures of BG24 variants bound to Envs with CD4bs glycans present provide insights into N-glycan accommodation, including structural modes of light chain adaptations in the presence of the N276 glycan. Together, these findings reveal Env regions critical for germline antibody recognition and potential sites to alter in immunogen design. | |||||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 7ugm.cif.gz | 180.9 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7ugm.ent.gz | 140.5 KB | Display | PDB format |
PDBx/mmJSON format | 7ugm.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ug/7ugm ftp://data.pdbj.org/pub/pdb/validation_reports/ug/7ugm | HTTPS FTP |
---|
-Related structure data
Related structure data | 7ugnC 7ugoC 7ugpC 7ugqC 7uceS S: Starting model for refinement C: citing same article (ref.) |
---|
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Antibody | Mass: 24003.961 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
---|---|
#2: Antibody | Mass: 22191.473 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: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.75 Å3/Da / Density % sol: 55.32 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / Details: 20% PEG 3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 21, 2019 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.4→38 Å / Num. obs: 101139 / % possible obs: 100 % / Redundancy: 19.7 % / CC1/2: 0.99 / Net I/σ(I): 11 |
Reflection shell | Resolution: 1.4→38 Å / Num. unique obs: 101139 / CC1/2: 0.99 |
-Processing
Software |
| ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 7UCE Resolution: 1.4→38 Å / Cross valid method: FREE R-VALUE
| ||||||||||||||||||
Displacement parameters | Biso max: 75.27 Å2 / Biso mean: 25.3402 Å2 / Biso min: 10.3 Å2 | ||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.4→38 Å
|