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- EMDB-73110: RRr20_wk72_07 Fab in complex with BG505 MD39 SOSIP and RM20A3 Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-73110
TitleRRr20_wk72_07 Fab in complex with BG505 MD39 SOSIP and RM20A3 Fab
Map datasharpened map
Sample
  • Complex: RRr20_wk72_07 Fab in complex with BG505 MD39 SOSIP and RM20A3 Fab
    • Protein or peptide: RM20A3 Fab heavy chain
    • Protein or peptide: RRr20_wk72_07 Fab heavy chain
    • Protein or peptide: RM20A3 light chain
    • Protein or peptide: RRr20_wk72_07 light chain
    • Protein or peptide: BG505 MD39 SOSIP gp120
    • Protein or peptide: BG505 MD39 SOSIP gp41
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsHIV-1 / Env / NHP / V3 glycan / BG18 / germline targeting / VIRAL PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / symbiont-mediated perturbation of host defense response / 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 ...positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / symbiont-mediated perturbation of host defense response / 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 / membrane / identical protein binding
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 speciesHuman immunodeficiency virus 1 / Macaca mulatta (Rhesus monkey)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 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)UM1 AI144462 United States
CitationJournal: Nature / Year: 2026
Title: Vaccination elicits HIV broadly neutralizing antibodies in primates.
Authors: Jon M Steichen / Patrick J Madden / Claudia T Flynn / Swastik Phulera / Monolina Shil / Oleksandr Kalyuzhniy / Alessia Liguori / Carolyne Kifude / Leigh M Sewall / Christopher A Cottrell / ...Authors: Jon M Steichen / Patrick J Madden / Claudia T Flynn / Swastik Phulera / Monolina Shil / Oleksandr Kalyuzhniy / Alessia Liguori / Carolyne Kifude / Leigh M Sewall / Christopher A Cottrell / Krystal M Ma / Sabyasachi Baboo / Jolene K Diedrich / Katherine McKenney / Allan C deCamp / Diane G Carnathan / Ivy Phung / Parham Ramezani-Rad / Ester Marina-Zárate / Brian Freeman / Zhenfei Xie / Jeong Hyun Lee / Troy Sincomb / Nicole Phelps / Danny Lu / Diana Goodwin / Ryan Tingle / Yumiko Adachi / Nushin Alavi / Jenny Tran / Andy S Tran / Alyne Nascimento / Catherine Sovie / Daniel L V Bader / Hannah Voic / Xiaoya Zhou / Grace Pixton / Agnes Walsh / Mariane B Melo / Torben Schiffner / Facundo D Batista / Dennis R Burton / Darrell J Irvine / James C Paulson / John R Yates / Gabriel Ozorowski / Andrew B Ward / Guido Silvestri / Shane Crotty / William R Schief /
Abstract: The high antigenic diversity of HIV has been a major obstacle to development of a broadly protective vaccine. Nevertheless, protective HIV broadly neutralizing antibodies (bnAbs) exist and have been ...The high antigenic diversity of HIV has been a major obstacle to development of a broadly protective vaccine. Nevertheless, protective HIV broadly neutralizing antibodies (bnAbs) exist and have been proposed as templates for vaccine development. Germline targeting is a conceptually radical vaccine design approach to elicit bnAbs, aiming to prime rare bnAb-precursor B cells possessing predetermined human genetic and structural features shared with template bnAbs, and then guide B cell affinity maturation to potent bnAb evolution with heterologous boosters. Although the approach has shown promise in clinical and preclinical studies, it faces many immunological challenges and, to date, has not succeeded in generating bnAbs in humans or non-transgenic animals. Here we report testing of an adjuvanted protein germline-targeting vaccine in outbred non-human primates. The vaccine generated bnAb-class memory B cells and sera capable of neutralizing diverse HIV clinical isolates. bnAb lineages were generated in at least 50% of animals, achieving up to 67% neutralization breadth compared with the reference bnAb. Vaccine-induced bnAbs exhibited precise structural mimicry of human bnAb interactions with HIV envelope (Env), matching the germline-targeting predictions. Furthermore, serum bnAb activity developed in 44% of animals and in one instance reached titres expected to confer protection against diverse HIV isolates. These results demonstrate proof of principle that germline-targeting vaccines can reproducibly elicit prespecified classes of bnAbs to prespecified epitopes under endogenous conditions, supporting further optimization of this approach for HIV vaccine development.
History
DepositionOct 10, 2025-
Header (metadata) releaseJul 8, 2026-
Map releaseJul 8, 2026-
UpdateJul 15, 2026-
Current statusJul 15, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_73110.png

Downloads & links

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Map

FileDownload / File: emd_73110.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationsharpened map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.04 Å/pix.
x 400 pix.
= 417.6 Å		1.04 Å/pix.
x 400 pix.
= 417.6 Å		1.04 Å/pix.
x 400 pix.
= 417.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.044 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.12
Minimum - Maximum-0.58343583 - 1.1875777
Average (Standard dev.)0.00016953243 (±0.02330108)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 417.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_73110_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map A

Fileemd_73110_half_map_1.map
Annotationhalf map A
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map B

Fileemd_73110_half_map_2.map
Annotationhalf map B
Projections & Slices
AxesZYX

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Histogram (log scale)

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Sample components

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Entire : RRr20_wk72_07 Fab in complex with BG505 MD39 SOSIP and RM20A3 Fab

EntireName: RRr20_wk72_07 Fab in complex with BG505 MD39 SOSIP and RM20A3 Fab
Components
  • Complex: RRr20_wk72_07 Fab in complex with BG505 MD39 SOSIP and RM20A3 Fab
    • Protein or peptide: RM20A3 Fab heavy chain
    • Protein or peptide: RRr20_wk72_07 Fab heavy chain
    • Protein or peptide: RM20A3 light chain
    • Protein or peptide: RRr20_wk72_07 light chain
    • Protein or peptide: BG505 MD39 SOSIP gp120
    • Protein or peptide: BG505 MD39 SOSIP gp41
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: RRr20_wk72_07 Fab in complex with BG505 MD39 SOSIP and RM20A3 Fab

SupramoleculeName: RRr20_wk72_07 Fab in complex with BG505 MD39 SOSIP and RM20A3 Fab
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6
Source (natural)Organism: Human immunodeficiency virus 1

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Macromolecule #1: RM20A3 Fab heavy chain

MacromoleculeName: RM20A3 Fab heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Macaca mulatta (Rhesus monkey)
Molecular weightTheoretical: 24.194145 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: EVQLVETGGG LVQPGGSLKL SCRASGYTFS SFAMSWVRQA PGKGLEWVSL INDRGGLTFY VDSVKGRFTI SRDNSKNTLS LQMHSLRDG DTAVYYCATG GMSSALQSSK YYFDFWGQGA LVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS ...String:
EVQLVETGGG LVQPGGSLKL SCRASGYTFS SFAMSWVRQA PGKGLEWVSL INDRGGLTFY VDSVKGRFTI SRDNSKNTLS LQMHSLRDG DTAVYYCATG GMSSALQSSK YYFDFWGQGA LVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKKVEPKSC D

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Macromolecule #2: RRr20_wk72_07 Fab heavy chain

MacromoleculeName: RRr20_wk72_07 Fab heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Macaca mulatta (Rhesus monkey)
Molecular weightTheoretical: 24.736777 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QVQLQESGPA LVKPSETLSL TCSISGDSDS GRHEWNWIRQ APGKGLEWIG DIHGNSGVTK YNPSLQSRVT ISKDMSKSQF SLRLRSVTA ADTATYYCAR ARIIIFGVVA LGETYYSGLD SWGQGVGVIV SSASTKGPSV FPLAPSSKST SGGTAALGCL V KDYFPEPV ...String:
QVQLQESGPA LVKPSETLSL TCSISGDSDS GRHEWNWIRQ APGKGLEWIG DIHGNSGVTK YNPSLQSRVT ISKDMSKSQF SLRLRSVTA ADTATYYCAR ARIIIFGVVA LGETYYSGLD SWGQGVGVIV SSASTKGPSV FPLAPSSKST SGGTAALGCL V KDYFPEPV TVSWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKK VEPKSC

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Macromolecule #3: RM20A3 light chain

MacromoleculeName: RM20A3 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Macaca mulatta (Rhesus monkey)
Molecular weightTheoretical: 22.82715 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: ALTQPPSVSG SPGQSVTISC TGTSSDIGSY NYVSWYQQHP GKAPKLMIYD VTQRPSGVSD RFSGSKSGNT ASLTISGLQA DDEADYYCS AYAGRQTFYI FGGGTRLTVL GQPKAAPSVT LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK A GVETTTPS ...String:
ALTQPPSVSG SPGQSVTISC TGTSSDIGSY NYVSWYQQHP GKAPKLMIYD VTQRPSGVSD RFSGSKSGNT ASLTISGLQA DDEADYYCS AYAGRQTFYI FGGGTRLTVL GQPKAAPSVT LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK A GVETTTPS KQSNNKYAAS SYLSLTPEQW KSHRSYSCQV THEGSTVEKT VAPTECS

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Macromolecule #4: RRr20_wk72_07 light chain

MacromoleculeName: RRr20_wk72_07 light chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Macaca mulatta (Rhesus monkey)
Molecular weightTheoretical: 22.950398 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SYELTQSRSV SVSPGQTARI TCGGATLARE NVHWYQQKPP QAPVLVINTN TERPSGIPER FSGSKSGNTA TLTISGVEAG DEADYYCQV WHINNAHVFF GGGTRLTVLG QPKAAPSVTL FPPSSEELQA NKATLVCLIS DFYPGAVTVA WKADSSPVKA G VETTTPSK ...String:
SYELTQSRSV SVSPGQTARI TCGGATLARE NVHWYQQKPP QAPVLVINTN TERPSGIPER FSGSKSGNTA TLTISGVEAG DEADYYCQV WHINNAHVFF GGGTRLTVLG QPKAAPSVTL FPPSSEELQA NKATLVCLIS DFYPGAVTVA WKADSSPVKA G VETTTPSK QSNNKYAASS YLSLTPEQWK SHRSYSCQVT HEGSTVEKTV APTECS

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Macromolecule #5: BG505 MD39 SOSIP gp120

MacromoleculeName: BG505 MD39 SOSIP gp120 / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 57.652625 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKRGLCCVLL LCGAVFVSPS QEIHARFRRG ARAENLWVTV YYGVPVWKDA ETTLFCASDA KAYETEKHNV WATHACVPTD PNPQEIHLE NVTEEFNMWK NNMVEQMHED IISLWDQSLK PCVKLTPLCV TLQCTNVTNN ITDDMRGELK NCSFNMTTEL R DKKQKVYS ...String:
MKRGLCCVLL LCGAVFVSPS QEIHARFRRG ARAENLWVTV YYGVPVWKDA ETTLFCASDA KAYETEKHNV WATHACVPTD PNPQEIHLE NVTEEFNMWK NNMVEQMHED IISLWDQSLK PCVKLTPLCV TLQCTNVTNN ITDDMRGELK NCSFNMTTEL R DKKQKVYS LFYRLDVVQI NENQGNRSNN SNKEYRLINC NTSAITQACP KVSFEPIPIH YCAPAGFAIL KCKDKKFNGT GP CPSVSTV QCTHGIKPVV STQLLLNGSL AEEEVIIRSE NITNNAKNIL VQLNTPVQIN CTRPNNNTVK SIRIGPGQAF YYT GDIIGD IRQAHCNVSK ATWNETLGKV VKQLRKHFGN NTIIRFAQSS GGDLEVTTHS FNCGGEFFYC NTSGLFNSTW ISNT SVQGS NSTGSNDSIT LPCRIKQIIN MWQRIGQAMY APPIQGVIRC VSNITGLILT RDGGSTNSTT ETFRPGGGDM RDNWR SELY KYKVVKIEPL GVAPTRCKRR VVGRRRRRR

UniProtKB: Envelope glycoprotein gp160

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Macromolecule #6: BG505 MD39 SOSIP gp41

MacromoleculeName: BG505 MD39 SOSIP gp41 / type: protein_or_peptide / ID: 6 / 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 #10: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 10 / 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

Concentration3.9 mg/mL
BufferpH: 7.4
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
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: FEI FALCON IV (4k x 4k) / Average electron dose: 45.0 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: 0.8 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL / In silico model: cryoSPARC ab initio
Final reconstructionApplied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 26959
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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