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- EMDB-70395: Ab1999 in complex with HIV-1 Env RC1 -

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Basic information

Entry
Database: EMDB / ID: EMD-70395
TitleAb1999 in complex with HIV-1 Env RC1
Map data
Sample
  • Complex: Antibody Ab1999 Fab in complex with HIV-1 Env RC1
    • Protein or peptide: Ab1999 Fab Heavy Chain variable region
    • Protein or peptide: Ab1999 Fab Light Chain variable region
    • Protein or peptide: Envelope glycoprotein gp120
    • Protein or peptide: Transmembrane protein gp41
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsHIV-1 Env / antibody / VIRAL PROTEIN
Function / homology
Function and homology information


symbiont-mediated perturbation of host defense response / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell ...symbiont-mediated perturbation of host defense response / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / structural molecule activity / identical protein binding / membrane
Similarity search - Function
Envelope glycoprotein Gp160 / Retroviral envelope protein / Retroviral envelope protein GP41-like / Gp120 core superfamily / Envelope glycoprotein GP120 / Human immunodeficiency virus 1, envelope glycoprotein Gp120
Similarity search - Domain/homology
Envelope glycoprotein gp160
Similarity search - Component
Biological speciesHomo sapiens (human) / Macaca mulatta (Rhesus monkey) / Human immunodeficiency virus 1
Methodsingle particle reconstruction / cryo EM / Resolution: 3.94 Å
AuthorsLin ZJ / Cui J / Du J / Relano-Rodriguez I / Escolano A / Pallesen J
Funding support United States, 1 items
OrganizationGrant numberCountry
Bill & Melinda Gates Foundation United States
CitationJournal: Nat Immunol / Year: 2026
Title: Rapid elicitation of neutralizing Asn332-glycan-independent antibodies to the V3-glycan epitope of HIV-1 Env in nonhuman primates.
Authors: Ignacio Relano-Rodriguez / Jianqiu Du / Zi Jie Lin / Margaret Kerwin / Marta Tarquis-Medina / Eduardo Urbano / Jiayan Cui / Meagan Watkins / Christy L Lavine / Peng Zhao / Rumi Habib / Colby ...Authors: Ignacio Relano-Rodriguez / Jianqiu Du / Zi Jie Lin / Margaret Kerwin / Marta Tarquis-Medina / Eduardo Urbano / Jiayan Cui / Meagan Watkins / Christy L Lavine / Peng Zhao / Rumi Habib / Colby Agostino / Sukanya Ghosh / Joyce Park / Caroline Boroughs / Agnes A Walsh / Mariane B Melo / Niharika Shukla / George M Shaw / Beatrice H Hahn / Darrell J Irvine / Lance Wells / David B Weiner / Michael S Seaman / Daniel W Kulp / Ronald S Veazey / Jesper Pallesen / Amelia Escolano /
Abstract: Sequential immunization is a promising approach to elicit broadly neutralizing antibodies (bNAbs) against the HIV-1 Envelope (Env). However, available protocols are inefficient and involve multiple ...Sequential immunization is a promising approach to elicit broadly neutralizing antibodies (bNAbs) against the HIV-1 Envelope (Env). However, available protocols are inefficient and involve multiple immunizations over long periods of time. Here, we present WIN332, a new engineered Env immunogen that induces a new class of Asn332-glycan-independent antibodies to the conserved V3-glycan epitope of Env with low inhibitory activity indicative of a neutralization activity after a single bolus immunization in nonhuman primates. WIN332 binds to precursors of canonical human Asn332-glycan-dependent (type-I) V3-glycan bNAbs but also of a first-of-its-class Asn332-glycan-independent (type-II) V3-glycan bNAb. A single immunization elicits low inhibitory serum and monoclonal antibodies that are boosted and affinity matured with a heterologous immunogen. Electron microscopy polyclonal epitope mapping analysis of serum antibodies, antibody cloning and cryogenic electron microscopy analysis reveals that WIN332 elicits Asn332-glycan-independent antibodies with striking sequence and binding similarities with the most potent human type-I and type-II V3-glycan bNAbs. Thus, WIN332 is a promising vaccine candidate to streamline V3-glycan bNAb elicitation.
History
DepositionApr 28, 2025-
Header (metadata) releaseFeb 11, 2026-
Map releaseFeb 11, 2026-
UpdateFeb 11, 2026-
Current statusFeb 11, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_70395.png

Downloads & links

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Map

FileDownload / File: emd_70395.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.95 Å/pix.
x 400 pix.
= 380. Å		0.95 Å/pix.
x 400 pix.
= 380. Å		0.95 Å/pix.
x 400 pix.
= 380. Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.95 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.176
Minimum - Maximum-0.60374093 - 1.0191787
Average (Standard dev.)-0.00028824882 (±0.018456534)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 380.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_70395_msk_1.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_70395_half_map_1.map
Projections & Slices
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Histogram

Histogram (log scale)

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Half map: #1

Fileemd_70395_half_map_2.map
Projections & Slices
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Histogram (log scale)

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Sample components

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Entire : Antibody Ab1999 Fab in complex with HIV-1 Env RC1

EntireName: Antibody Ab1999 Fab in complex with HIV-1 Env RC1
Components
  • Complex: Antibody Ab1999 Fab in complex with HIV-1 Env RC1
    • Protein or peptide: Ab1999 Fab Heavy Chain variable region
    • Protein or peptide: Ab1999 Fab Light Chain variable region
    • Protein or peptide: Envelope glycoprotein gp120
    • Protein or peptide: Transmembrane protein gp41
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Antibody Ab1999 Fab in complex with HIV-1 Env RC1

SupramoleculeName: Antibody Ab1999 Fab in complex with HIV-1 Env RC1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Ab1999 Fab Heavy Chain variable region

MacromoleculeName: Ab1999 Fab Heavy Chain variable region / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Macaca mulatta (Rhesus monkey)
Molecular weightTheoretical: 14.014623 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QVQLQESGPG LVKPSETLSL TCAVSGGSIS DDYSWSWIRQ PPGKGLEWIG YIYGSGGGTN YNPSLKNRVT ISIDTSKNQF SLKLSSVTA ADTAVYYCAR IFAFITVFGV VTPEDNWFDV WGPGVLVTVS S

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Macromolecule #2: Ab1999 Fab Light Chain variable region

MacromoleculeName: Ab1999 Fab Light Chain variable region / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Macaca mulatta (Rhesus monkey)
Molecular weightTheoretical: 11.58576 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
DIQMTQSPSS LSASVGDRVT ITCRASQSIN NYLHWYQQRA GEAPKLLIYA ASALQTGVPS RFSGSGSGTD FTLTISSLQP EDVATYYCQ HSYGTPYSFG QGTKVEIK

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Macromolecule #3: Envelope glycoprotein gp120

MacromoleculeName: Envelope glycoprotein gp120 / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 54.093504 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GSNLWVTVYY GVPVWKDAET TLFCASDAKA YETEKHNVWA THACVPTDPN PQEIHLENVT EEFNMWKNNM VEQMHEDIIS LWDQSLKPC VKLTPLCVTL QCTNYAPNLL SNMRGELKQC SFNMTTELRD KKQKVYSLFY RLDVVQINEN QGNRSNNSNK E YRLINCNT ...String:
GSNLWVTVYY GVPVWKDAET TLFCASDAKA YETEKHNVWA THACVPTDPN PQEIHLENVT EEFNMWKNNM VEQMHEDIIS LWDQSLKPC VKLTPLCVTL QCTNYAPNLL SNMRGELKQC SFNMTTELRD KKQKVYSLFY RLDVVQINEN QGNRSNNSNK E YRLINCNT SAITQACPKV SFEPIPIHYC APAGFAILKC KDKKFNGTGP CPSVSTVQCT HGIKPVVSTQ LLLNGSLAEE EV IIRSENI TNNAKNILVQ LNTPVQINCT RPNNNTVKSI RIGPGQAFYY FGDIIGDIRM AHCNVSKATW NETLGKVVKQ LRK HFGNNT IIRFAQSSGG DLEVTTHSFN CGGEFFYCNT SGLFNSTWIS NTSVQGSNST GSNDSIVLPC RIKQIINMWQ RIGQ AMYAP PIQGVIRCVS NITGLILTRD GGSTNSTTET FRPGGGDMRD NWRSELYKYK VVKIEPLGVA PTRCKRRVVG RRRRR R

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Macromolecule #4: Transmembrane protein gp41

MacromoleculeName: Transmembrane protein gp41 / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 17.134324 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
AVGIGAVSLG FLGAAGSTMG AASMTLTVQA RNLLSGIVQQ QSNLLRAPEP QQHLLKDTHW GIKQLQARVL AVEHYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNRNLS EIWDNMTWLQ WDKEISNYTQ IIYGLLEESQ NQQEKNEQDL LALD

UniProtKB: Envelope glycoprotein gp160

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Macromolecule #9: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 9 / Number of copies: 23 / 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: 7.6 / Details: 1X PBS
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GRAPHENE OXIDE / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec.
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 150000

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Image processing

CTF correctionType: NONE
Startup modelType of model: NONE
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.94 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.4) / Number images used: 94081
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.4) / Software - details: Ab initio reconstruction
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.4) / Software - details: Non-Uniform Refinement
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelPDB ID:

6orn


Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementProtocol: FLEXIBLE FIT
Output model

PDB-9oed:
Ab1999 in complex with HIV-1 Env RC1

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