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- EMDB-72735: HIV-1 Env Q23 NFL TD CC3+ in complex with NHP Q9 V2-apex polyclon... -

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Basic information

Entry
Database: EMDB / ID: EMD-72735
TitleHIV-1 Env Q23 NFL TD CC3+ in complex with NHP Q9 V2-apex polyclonal antibody Fabs isolated post-2 immunizations
Map datamain map
Sample
  • Complex: HIV-1 Env Q23 NFL TD CC3+ in complex with NHP Q9 V2-apex polyclonal antibody Fabs isolated post-2 immunizations
    • Complex: HIV-1 Env Q23 NFL TD CC3+
Keywordsneutralizing antibody / HIV vaccine / macaque / non-human primate / EMPEM / VIRAL PROTEIN
Biological speciesMacaca mulatta (Rhesus monkey) / Human immunodeficiency virus 1
Methodsingle particle reconstruction / negative staining / Resolution: 30.0 Å
AuthorsLee W-H / Ozorowski G / Ward AB
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)P01 AI157299 United States
CitationJournal: bioRxiv / Year: 2025
Title: HIV Env trimers elicit NHP apex cross-neutralizing antibodies mimicking human bNAbs.
Authors: Javier Guenaga / Monika Adori / Shridhar Bale / Swastik Phulera / Ioannis Zygouras / Fabian-Alexander Schleich / Xaquin Castro Dopico / Sashank Agrawal / Miyo Ota / Richard Wilson / Jocelyn ...Authors: Javier Guenaga / Monika Adori / Shridhar Bale / Swastik Phulera / Ioannis Zygouras / Fabian-Alexander Schleich / Xaquin Castro Dopico / Sashank Agrawal / Miyo Ota / Richard Wilson / Jocelyn Cluff / Tamar Dzvelaia / Marco Mandolesi / Agnes Walsh / Mariane B Melo / Laurent Verkoczy / Darrell J Irvine / Martin Corcoran / Ian A Wilson / Diane Carnathan / Guido Silvestri / Andrew B Ward / Gabriel Ozorowski / Gunilla B Karlsson Hedestam / Richard T Wyatt
Abstract: As a chronically replicating virus, HIV has evolved extreme sequence variability and effective shielding of functionally constrained spike protein determinants by host-derived glycans. Broadly ...As a chronically replicating virus, HIV has evolved extreme sequence variability and effective shielding of functionally constrained spike protein determinants by host-derived glycans. Broadly neutralizing antibodies (bNAbs), though rare, can be isolated from people living with HIV, revealing conserved Env sites as key targets for vaccine development. One such target is the apex of the envelope glycoprotein (Env) spike. Here, we identified a vaccination strategy using heterologous HIV Env trimers covalently coupled to liposomes for multivalent display that resulted in the elicitation of cross-neutralizing HIV serum antibody responses in all immunized non-human primates (NHPs). Critically, we isolated a set of monoclonal antibodies (mAbs) that cross-neutralized multiple divergent HIV clinical isolates. High-resolution cryoEM structural analysis of mAbs from three different NHPs demonstrated that they targeted the Env trimer apex in a manner remarkably similar to that of the human infection-elicited, apex-directed bNAb PG9, representing a substantial advance in HIV vaccine development.
History
DepositionSep 16, 2025-
Header (metadata) releaseOct 22, 2025-
Map releaseOct 22, 2025-
UpdateOct 22, 2025-
Current statusOct 22, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_72735.png

Downloads & links

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Map

FileDownload / File: emd_72735.map.gz / Format: CCP4 / Size: 3.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationmain map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
3.78 Å/pix.
x 96 pix.
= 362.88 Å		3.78 Å/pix.
x 96 pix.
= 362.88 Å		3.78 Å/pix.
x 96 pix.
= 362.88 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 3.78 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.018
Minimum - Maximum-0.04424376 - 0.06910789
Average (Standard dev.)-0.000048263755 (±0.0035485125)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions969696
Spacing969696
CellA=B=C: 362.88 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: half map B

Fileemd_72735_half_map_1.map
Annotationhalf map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map A

Fileemd_72735_half_map_2.map
Annotationhalf map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : HIV-1 Env Q23 NFL TD CC3+ in complex with NHP Q9 V2-apex polyclon...

EntireName: HIV-1 Env Q23 NFL TD CC3+ in complex with NHP Q9 V2-apex polyclonal antibody Fabs isolated post-2 immunizations
Components
  • Complex: HIV-1 Env Q23 NFL TD CC3+ in complex with NHP Q9 V2-apex polyclonal antibody Fabs isolated post-2 immunizations
    • Complex: HIV-1 Env Q23 NFL TD CC3+

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Supramolecule #1: HIV-1 Env Q23 NFL TD CC3+ in complex with NHP Q9 V2-apex polyclon...

SupramoleculeName: HIV-1 Env Q23 NFL TD CC3+ in complex with NHP Q9 V2-apex polyclonal antibody Fabs isolated post-2 immunizations
type: complex / ID: 1 / Parent: 0
Details: Polyclonal IgG isolated from serum and digested to Fab using papain
Source (natural)Organism: Macaca mulatta (Rhesus monkey)

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Supramolecule #2: HIV-1 Env Q23 NFL TD CC3+

SupramoleculeName: HIV-1 Env Q23 NFL TD CC3+ / type: complex / ID: 2 / Parent: 1
Source (natural)Organism: Human immunodeficiency virus 1

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Experimental details

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Structure determination

Methodnegative staining
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration0.03 mg/mL
BufferpH: 7.4
StainingType: NEGATIVE / Material: Nano-W
GridModel: Homemade / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE

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Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 25.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER

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Image processing

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

6v0r


Details: PDB coordinates converted to map using UCSF Chimera molmap and low pass filtered to 40 Angstrom
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 30.0 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: RELION (ver. 4.0) / Number images used: 9486
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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