- EMDB-26494: Cryo-EM map of BG24 Fabs with an inferred germline light chain an... -
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Basic information
Entry
Database: EMDB / ID: EMD-26494
Title
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 2
Map data
Sample
Complex: 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 2
Biological species
Human immunodeficiency virus 1
Method
single particle reconstruction / cryo EM / Resolution: 4.6 Å
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
HIVRAD P01 AI100148
United States
Bill & Melinda Gates Foundation
CAVD INV-002143
United States
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.
Entire : Cryo-EM map of BG24 Fabs with an inferred germline light chain an...
Entire
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 2
Components
Complex: 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 2
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Supramolecule #1: Cryo-EM map of BG24 Fabs with an inferred germline light chain an...
Supramolecule
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 2 type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#6
Source (natural)
Organism: Human immunodeficiency virus 1
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Experimental details
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Structure determination
Method
cryo EM
Processing
single particle reconstruction
Aggregation state
particle
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Sample preparation
Buffer
pH: 8
Vitrification
Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV
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Electron microscopy
Microscope
FEI TALOS ARCTICA
Image recording
Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beam
Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
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