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- EMDB-70666: Cryo-EM structure of vaccine-elicited antibody T6_P_H03 in comple... -

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Basic information

Entry
Database: EMDB / ID: EMD-70666
TitleCryo-EM structure of vaccine-elicited antibody T6_P_H03 in complex with HIV Env trimer Q23-APEX-GT1
Map data
Sample
  • Complex: T6_P_H03 Fab in complex with HIV envelope trimer Q23-APEX-GT1
    • Protein or peptide: T6_P_H03 heavy chain
    • Protein or peptide: T6_P_H03 light chain
    • Protein or peptide: HIV Env gp120
    • Protein or peptide: HIV Env gp41 ectodomain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Keywordsimmune complex / neutralizing antibody / V2 apex / mouse model / VIRAL PROTEIN
Biological speciesHuman immunodeficiency virus 1 / Mus musculus (house mouse) / Human immunodeficiency virus type 1
Methodsingle particle reconstruction / cryo EM / Resolution: 3.5 Å
AuthorsRoark RS / Shapiro LS / Kwong PD
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) United States
CitationJournal: Sci Immunol / Year: 2026
Title: Rapidly acquired HIV-1 neutralization breadth in a rhesus V2 apex knockin mouse model after a single bolus immunization.
Authors: Amrit Raj Ghosh / Rumi Habib / Nitesh Mishra / Ryan S Roark / Madhav Akauliya / Ali A Albowaidey / Joel D Allen / Khaled Amereh / Gabriel Avillion / Maria Bottermann / Bo Liang / Namit ...Authors: Amrit Raj Ghosh / Rumi Habib / Nitesh Mishra / Ryan S Roark / Madhav Akauliya / Ali A Albowaidey / Joel D Allen / Khaled Amereh / Gabriel Avillion / Maria Bottermann / Bo Liang / Namit Chaudhary / Sean Callaghan / Jonathan Dye / Xuduo Li / Jordan R Ellis-Pugh / Rohan Roy Chowdhury / Nicole E James / Xiaotie Liu / Laura Maiorino / Paula M Villavicencio / Rebecca Nedellec / Prabhgun Oberoi / Kirsten J Sowers / Younghoon Park / Thavaleak Prum / Linette Rodriguez / Maria Ssozi / Jonathan L Torres / Agnes A Walsh / John E Warner / Stephanie R Weldon / Liling Xu / Kevin Wiehe / Max Crispin / Andrew B Ward / Usha Nair / Beatrice H Hahn / Dennis R Burton / Lawrence Shapiro / Peter D Kwong / Darrell J Irvine / Raiees Andrabi / George M Shaw / Facundo D Batista /
Abstract: Current immunization strategies to elicit broadly neutralizing antibodies (bnAbs) against HIV-1 generally propose complex, multiboost regimens. In rhesus macaques, simian-human immunodeficiency virus ...Current immunization strategies to elicit broadly neutralizing antibodies (bnAbs) against HIV-1 generally propose complex, multiboost regimens. In rhesus macaques, simian-human immunodeficiency virus (SHIV) infection rapidly drives the development of some bnAb classes sharing structural similarities with those in humans. Here, we generated a knockin (KI) mouse model with B cells bearing the unmutated common ancestor of a V2 apex-targeted bnAb lineage, V033-a. A single immunization with a germline-targeting native-like trimer, Q23-APEX-GT1, recapitulated the ontogeny of the mature rhesus bnAb in KI mice, including rare, disfavored somatic mutations. Resulting antibodies exhibited potent neutralization against a broad panel of heterologous HIV-1 strains. Boosting with Env escape mutant trimers further improved breadth and potency, and cryo-electron microscopy analysis revealed the structural basis for heterologous neutralization breadth. Nonhuman primate and mouse models combined with structure can serve as a platform for identifying and validating immunogens that streamline HIV vaccination regimens.
History
DepositionMay 16, 2025-
Header (metadata) releaseNov 12, 2025-
Map releaseNov 12, 2025-
UpdateFeb 25, 2026-
Current statusFeb 25, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_70666.png

Downloads & links

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Map

FileDownload / File: emd_70666.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 384 pix.
= 318.72 Å		0.83 Å/pix.
x 384 pix.
= 318.72 Å		0.83 Å/pix.
x 384 pix.
= 318.72 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.09
Minimum - Maximum-0.14405657 - 0.3954819
Average (Standard dev.)-0.00009607754 (±0.014188132)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 318.72 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_70666_half_map_1.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_70666_half_map_2.map
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Sample components

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Entire : T6_P_H03 Fab in complex with HIV envelope trimer Q23-APEX-GT1

EntireName: T6_P_H03 Fab in complex with HIV envelope trimer Q23-APEX-GT1
Components
  • Complex: T6_P_H03 Fab in complex with HIV envelope trimer Q23-APEX-GT1
    • Protein or peptide: T6_P_H03 heavy chain
    • Protein or peptide: T6_P_H03 light chain
    • Protein or peptide: HIV Env gp120
    • Protein or peptide: HIV Env gp41 ectodomain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: T6_P_H03 Fab in complex with HIV envelope trimer Q23-APEX-GT1

SupramoleculeName: T6_P_H03 Fab in complex with HIV envelope trimer Q23-APEX-GT1
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Human immunodeficiency virus 1

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Macromolecule #1: T6_P_H03 heavy chain

MacromoleculeName: T6_P_H03 heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 25.139137 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: EVQLVESGGG LAKPGGSLRL SCAASGFTFS NYWMNWVRQT PGKGLEWISG INSGGGSRSY ADSVMGRFII SRDNSKNTLS LQMNSLRAE DTAVYYCAKV DDDDYGYFDT VPGDLKKYYL KYWGRGVLVT VSSASTTPPS VYPLAPGSAA QTNSMVTLGC L VKGYFPEP ...String:
EVQLVESGGG LAKPGGSLRL SCAASGFTFS NYWMNWVRQT PGKGLEWISG INSGGGSRSY ADSVMGRFII SRDNSKNTLS LQMNSLRAE DTAVYYCAKV DDDDYGYFDT VPGDLKKYYL KYWGRGVLVT VSSASTTPPS VYPLAPGSAA QTNSMVTLGC L VKGYFPEP VTVTWNSGSL SSGVHTFPAV LQSDLYTLSS SVTVPSSTWP SETVTCNVAH PASSTKVDKK IVPRDCG

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Macromolecule #2: T6_P_H03 light chain

MacromoleculeName: T6_P_H03 light chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 23.481762 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DIQMTQSPSS LSASVGDKVT ITCQASQSIS SWLAWYQQKP GKAPKPLIYK ASSLESGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQ QYNSAPFSFG QGTEVEIKRT DAAPTVSIFP PSSEQLTSGG ASVVCFLNNF YPKDINVKWK IDGSERQNGV L NSWTDQDS ...String:
DIQMTQSPSS LSASVGDKVT ITCQASQSIS SWLAWYQQKP GKAPKPLIYK ASSLESGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQ QYNSAPFSFG QGTEVEIKRT DAAPTVSIFP PSSEQLTSGG ASVVCFLNNF YPKDINVKWK IDGSERQNGV L NSWTDQDS KDSTYSMSST LTLTKDEYER HNSYTCEATH KTSTSPIVKS FNRNEC

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Macromolecule #3: HIV Env gp120

MacromoleculeName: HIV Env gp120 / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus type 1
Molecular weightTheoretical: 56.731629 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARAENLW VTVYYGVPVW RDAETTLFCA SDAKAYETEK HNVWATHACV PTDPNPQEI HLDNVTEKFN MWKNNMVEQM HTDIISLWDQ SLKPCVKLTP LCVTLHCTNV TSVNTTGDRE ELKNCSFNMT T ELRDKRQK ...String:
MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARAENLW VTVYYGVPVW RDAETTLFCA SDAKAYETEK HNVWATHACV PTDPNPQEI HLDNVTEKFN MWKNNMVEQM HTDIISLWDQ SLKPCVKLTP LCVTLHCTNV TSVNTTGDRE ELKNCSFNMT T ELRDKRQK VYSLFYRLDI VPINENQGSE YRLINCNTSA CTQACPKVSF EPIPIHYCAP AGFAILKCKD EGFNGTGLCK NV STVQCTH GIKPVVSTQL LLNGSLAEKN ITIRSENITN NAKIIIVQLV QPVTIKCIRP NNYTRKSIRI GPGQAFYAMG DII GDIRQA HCNVSRSRWN KTLQEVAEKL RTYFGNKTII FANSSGGDLE ITTHSFNCGG EFFYCNTSGL FNSTWYVNST WNDT DSTQE SNDTITLPCR IKQIINMWQR AGQCMYAPPI PGVIKCESNI TGLLLTRDGG KDNNVNETFR PGGGDMRDNW RSELY KYKV VEIEPLGVAP TRCKRRVVE

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Macromolecule #4: HIV Env gp41 ectodomain

MacromoleculeName: HIV Env gp41 ectodomain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus type 1
Molecular weightTheoretical: 17.205666 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
AVGIGAVRRG FLGAAGSTMG AASITLTVQA RQLLSGIVQP QNNLLRAPEA QQHLLKLGVW GIKQLQARVL AVERYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNKSLD EIWNNMTWLQ WDKEIGNYTQ LIYRLIEESQ NQQEKNEKEL LALD

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Macromolecule #12: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 12 / Number of copies: 30 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5 / Details: PBS
VitrificationCryogen name: ETHANE / Chamber humidity: 100 %

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 58.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

9bnp

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 140657
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE

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