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Yorodumi- PDB-7ugp: Cryo-EM structure of BG24 Fabs with an inferred germline light ch... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7ugp | |||||||||
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Title | Cryo-EM structure of BG24 Fabs with an inferred germline light chain and 10-1074 Fabs in complex with HIV-1 Env immunogen BG505-SOSIPv4.1-GT1 containing the N276 gp120 glycan- Class 1 | |||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 Env / neutralizing antibody / CD4 binding site antibody / VIRAL PROTEIN / Germline / precursor / immunogen / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
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 / apoptotic process / host cell plasma membrane / virion membrane / structural molecule activity / plasma membrane Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.2 Å | |||||||||
Authors | Dam, K.A. / Bjorkman, P.J. | |||||||||
Funding support | United States, 2items
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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 |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7ugp.cif.gz | 544.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7ugp.ent.gz | 460.9 KB | Display | PDB format |
PDBx/mmJSON format | 7ugp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7ugp_validation.pdf.gz | 1.8 MB | Display | wwPDB validaton report |
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Full document | 7ugp_full_validation.pdf.gz | 1.8 MB | Display | |
Data in XML | 7ugp_validation.xml.gz | 84.4 KB | Display | |
Data in CIF | 7ugp_validation.cif.gz | 134.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ug/7ugp ftp://data.pdbj.org/pub/pdb/validation_reports/ug/7ugp | HTTPS FTP |
-Related structure data
Related structure data | 26493MC 7ugmC 7ugnC 7ugoC 7ugqC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Envelope glycoprotein ... , 2 types, 6 molecules ABCDEF
#1: Protein | Mass: 49860.875 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Details: Env mimic BG505-SOSIPv4.1-GT1 / Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Production host: Homo sapiens (human) / References: UniProt: Q2N0S5 #2: Protein | Mass: 14577.591 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Details: Env mimic BG505-SOSIPv4.1-GT1 / Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Production host: Homo sapiens (human) |
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-Antibody , 4 types, 12 molecules MNOGHIPQRJKL
#3: Antibody | Mass: 14791.433 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #4: Antibody | Mass: 13384.042 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #5: Antibody | Mass: 11701.023 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #6: Antibody | Mass: 11084.096 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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-Sugars , 4 types, 42 molecules
#7: Polysaccharide | Type: oligosaccharide / Mass: 1072.964 Da / Num. of mol.: 3 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: Sugar | ChemComp-NAG / |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Cryo-EM map of BG24 Fabs with an inferred germline light chain and 10-1074 Fabs in complex with HIV-1 Env immunogen BG505-SOSIPv4.1-GT1 containing the N276 gp120 glycan- Class 1 Type: COMPLEX / Entity ID: #1-#6 / Source: MULTIPLE SOURCES | |||||||||||||||
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Molecular weight | Experimental value: NO | |||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 8 | |||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1200 nm / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 4.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 23830 / Symmetry type: POINT |