- EMDB-41823: Cryo-EM structure of vaccine-elicited CD4 binding site antibody D... -
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Open data
ID or keywords:
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Basic information
Entry
Database: EMDB / ID: EMD-41823
Title
Cryo-EM structure of vaccine-elicited CD4 binding site antibody DH1285 bound to HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env
Map data
Rhesus macaque vaccine elicited CD4 binding site antibody DH1285 Fab bound to three CD4 binding sites on CH505TFchim.6R.SOSIP.664v4.1 Env.
Sample
Organelle or cellular component: A Complex of ectodomain of HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env with CD4 binding site antibody Dh1285 Fab in 1:3 ratio
Keywords
HIV-1 / CD4 binding site antibody / Vaccine elicited antibody / neutralizing antibody / IgG / Fab / DH1285 / VIRAL PROTEIN
Biological species
Human immunodeficiency virus 1
Method
single particle reconstruction / cryo EM / Resolution: 5.42 Å
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01 A1145687
United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
UM1 A1144371
United States
Citation
Journal: Cell / Year: 2024 Title: Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques. Authors: Kevin O Saunders / James Counts / Bhishem Thakur / Victoria Stalls / Robert Edwards / Kartik Manne / Xiaozhi Lu / Katayoun Mansouri / Yue Chen / Rob Parks / Maggie Barr / Laura Sutherland / ...Authors: Kevin O Saunders / James Counts / Bhishem Thakur / Victoria Stalls / Robert Edwards / Kartik Manne / Xiaozhi Lu / Katayoun Mansouri / Yue Chen / Rob Parks / Maggie Barr / Laura Sutherland / Joena Bal / Nicholas Havill / Haiyan Chen / Emily Machiele / Nolan Jamieson / Bhavna Hora / Megan Kopp / Katarzyna Janowska / Kara Anasti / Chuancang Jiang / Elizabeth Van Itallie / Sravani Venkatayogi / Amanda Eaton / Rory Henderson / Christopher Barbosa / S Munir Alam / Sampa Santra / Drew Weissman / M Anthony Moody / Derek W Cain / Ying K Tam / Mark Lewis / Wilton B Williams / Kevin Wiehe / David C Montefiori / Priyamvada Acharya / Barton F Haynes / Abstract: The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs ...The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs for many reasons, including the occlusion of CD4bs by glycans, expansion of appropriate naive B cells with immunogens, and selection of functional antibody mutations. Here, we demonstrate that immunization of macaques with a CD4bs-targeting immunogen elicits neutralizing bnAb precursors with structural and genetic features of CD4-mimicking bnAbs. Structures of the CD4bs nAb bound to HIV-1 Env demonstrated binding angles and heavy-chain interactions characteristic of all known human CD4-mimicking bnAbs. Macaque nAb were derived from variable and joining gene segments orthologous to the genes of human VH1-46-class bnAb. This vaccine study initiated in primates the B cells from which CD4bs bnAbs can derive, accomplishing the key first step in the development of an effective HIV-1 vaccine.
Entire : A Complex of ectodomain of HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env...
Entire
Name: A Complex of ectodomain of HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env with CD4 binding site antibody Dh1285 Fab in 1:3 ratio
Components
Organelle or cellular component: A Complex of ectodomain of HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env with CD4 binding site antibody Dh1285 Fab in 1:3 ratio
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Supramolecule #1: A Complex of ectodomain of HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env...
Supramolecule
Name: A Complex of ectodomain of HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env with CD4 binding site antibody Dh1285 Fab in 1:3 ratio type: organelle_or_cellular_component / ID: 1 / Parent: 0
Source (natural)
Organism: Human immunodeficiency virus 1
Molecular weight
Theoretical: 300 KDa
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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
Concentration
1.3 mg/mL
Buffer
pH: 8
Grid
Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
Vitrification
Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 298 K / Instrument: LEICA EM CPC
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Electron microscopy
Microscope
FEI TITAN KRIOS
Image recording
Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 59.1 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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