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- EMDB-74449: Q7M-675 Fab in complex with HIV-1 Env WITO NFL TD CC3+ -

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Basic information

Entry
Database: EMDB / ID: EMD-74449
TitleQ7M-675 Fab in complex with HIV-1 Env WITO NFL TD CC3+
Map datamain map
Sample
  • Complex: Q7M-675 Fab in complex with HIV-1 Env WITO NFL TD CC3+
KeywordsHIV-1 / macaque / non-human primate / NHP / V2-apex / neutralizing antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex / VIRAL PROTEIN
Biological speciesHuman immunodeficiency virus 1
Methodsingle particle reconstruction / cryo EM / Resolution: 4.3 Å
AuthorsPhulera S / 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: Nature / Year: 2026
Title: Vaccination generates broadly cross-neutralizing antibodies to the HIV Env apex.
Authors: Javier Guenaga / Monika Ádori / Shridhar Bale / Swastik Phulera / Ioannis Zygouras / Fabian-Alexander Schleich / Xaquin Castro Dopico / Sashank Agrawal / Miyo Ota / Richard Wilson / Jocelyn ...Authors: Javier Guenaga / Monika Ádori / Shridhar Bale / Swastik Phulera / Ioannis Zygouras / Fabian-Alexander Schleich / Xaquin Castro Dopico / Sashank Agrawal / Miyo Ota / Richard Wilson / Jocelyn Cluff / Tamar Dzvelaia / Marco Mandolesi / Wen-Hsin Lee / Agnes A 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, although rare, can be isolated from people living with HIV, revealing conserved envelope glycoprotein (Env) sites as key targets for vaccine development. One such target is the apex of the Env spike. Here we identify 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 trimer-liposome-immunized non-human primates. Critically, we isolated monoclonal antibodies from multiple macaques that cross-neutralize divergent HIV clinical isolates. High-resolution cryogenic electron microscopy structural analyses of monoclonal antibodies from four different macaques demonstrate that they target the Env trimer apex in a manner highly similar to that of the human-infection-elicited, apex-directed broadly neutralizing antibody PG9, representing a substantial advance in HIV vaccine development.
History
DepositionDec 12, 2025-
Header (metadata) releaseJun 17, 2026-
Map releaseJun 17, 2026-
UpdateJun 17, 2026-
Current statusJun 17, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_74449.map.gz / Format: CCP4 / Size: 512 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.)
0.72 Å/pix.
x 512 pix.
= 367.616 Å
0.72 Å/pix.
x 512 pix.
= 367.616 Å
0.72 Å/pix.
x 512 pix.
= 367.616 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.718 Å
Density
Contour LevelBy AUTHOR: 0.04
Minimum - Maximum-0.088152185 - 0.23754157
Average (Standard dev.)-0.000070111695 (±0.006246211)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 367.616 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_74449_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: half map B

Fileemd_74449_half_map_1.map
Annotationhalf map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: half map A

Fileemd_74449_half_map_2.map
Annotationhalf map A
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

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Sample components

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Entire : Q7M-675 Fab in complex with HIV-1 Env WITO NFL TD CC3+

EntireName: Q7M-675 Fab in complex with HIV-1 Env WITO NFL TD CC3+
Components
  • Complex: Q7M-675 Fab in complex with HIV-1 Env WITO NFL TD CC3+

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Supramolecule #1: Q7M-675 Fab in complex with HIV-1 Env WITO NFL TD CC3+

SupramoleculeName: Q7M-675 Fab in complex with HIV-1 Env WITO NFL TD CC3+
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Human immunodeficiency virus 1

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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

Concentration5 mg/mL
BufferpH: 7.4
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: TFS FALCON 4i (4k x 4k) / Average electron dose: 45.1 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL / In silico model: ab initio
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 4.3 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 24436
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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