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- EMDB-29731: Vaccine-elicited human antibody 2C09 in complex with HIV-1 envelo... -

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Basic information

Entry
Database: EMDB / ID: EMD-29731
TitleVaccine-elicited human antibody 2C09 in complex with HIV-1 envelope trimer BG505 DS-SOSIP
Map dataCryoSPARC map with C3 symmetry
Sample
  • Complex: HIV envelope trimer in complex with three copies of antibody Fab
    • Protein or peptide: Envelope glycoprotein BG505 DS-SOSIP gp41
    • Protein or peptide: Envelope glycoprotein BG505 DS-SOSIP gp120
    • Protein or peptide: Fab 2C09 heavy chain
    • Protein or peptide: Fab 2C09 light chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Keywordsantibody-antigen complex vaccine-elicited antibody fusion peptide strain specific / ANTIVIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / virus-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 ...positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / virus-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 / identical protein binding / plasma 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 / Envelope glycoprotein gp160
Similarity search - Component
Biological speciesHuman immunodeficiency virus 1 / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.81 Å
AuthorsWang S / 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: Cell Rep / Year: 2023
Title: HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide.
Authors: Shuishu Wang / Flavio Matassoli / Baoshan Zhang / Tracy Liu / Chen-Hsiang Shen / Tatsiana Bylund / Timothy Johnston / Amy R Henry / I-Ting Teng / Prabhanshu Tripathi / Jordan E Becker / ...Authors: Shuishu Wang / Flavio Matassoli / Baoshan Zhang / Tracy Liu / Chen-Hsiang Shen / Tatsiana Bylund / Timothy Johnston / Amy R Henry / I-Ting Teng / Prabhanshu Tripathi / Jordan E Becker / Anita Changela / Ridhi Chaudhary / Cheng Cheng / Martin Gaudinski / Jason Gorman / Darcy R Harris / Myungjin Lee / Nicholas C Morano / Laura Novik / Sijy O'Dell / Adam S Olia / Danealle K Parchment / Reda Rawi / Jesmine Roberts-Torres / Tyler Stephens / Yaroslav Tsybovsky / Danyi Wang / David J Van Wazer / Tongqing Zhou / Nicole A Doria-Rose / Richard A Koup / Lawrence Shapiro / Daniel C Douek / Adrian B McDermott / Peter D Kwong /
Abstract: Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers ...Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing antibodies has been reported in multiple vaccine-test species, though not in humans. To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the "DS-SOSIP"-stabilized envelope trimer from strain BG505, identifying two antibodies, N751-2C06.01 and N751-2C09.01 (named for donor-lineage.clone), that neutralize the autologous tier-2 strain, BG505. Though derived from distinct lineages, these antibodies form a reproducible antibody class that targets the HIV-1 fusion peptide. Both antibodies are highly strain specific, which we attribute to their partial recognition of a BG505-specific glycan hole and to their binding requirements for a few BG505-specific residues. Prefusion-stabilized envelope trimers can thus elicit autologous tier-2 neutralizing antibodies in humans, with initially identified neutralizing antibodies recognizing the fusion-peptide site of vulnerability.
History
DepositionFeb 10, 2023-
Header (metadata) releaseJul 12, 2023-
Map releaseJul 12, 2023-
UpdateJul 26, 2023-
Current statusJul 26, 2023Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_29731.png

Downloads & links

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Map

FileDownload / File: emd_29731.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationCryoSPARC map with C3 symmetry
Voxel sizeX=Y=Z: 1.11 Å
Density
Contour LevelBy EMDB: 0.12
Minimum - Maximum-0.33698288 - 0.9938623
Average (Standard dev.)-0.00023974695 (±0.021277098)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 399.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: cryoSPARC half map A

Fileemd_29731_half_map_1.map
AnnotationcryoSPARC half map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: crySPARC half map B

Fileemd_29731_half_map_2.map
AnnotationcrySPARC half map B
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 envelope trimer in complex with three copies of antibody Fab

EntireName: HIV envelope trimer in complex with three copies of antibody Fab
Components
  • Complex: HIV envelope trimer in complex with three copies of antibody Fab
    • Protein or peptide: Envelope glycoprotein BG505 DS-SOSIP gp41
    • Protein or peptide: Envelope glycoprotein BG505 DS-SOSIP gp120
    • Protein or peptide: Fab 2C09 heavy chain
    • Protein or peptide: Fab 2C09 light chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: HIV envelope trimer in complex with three copies of antibody Fab

SupramoleculeName: HIV envelope trimer in complex with three copies of antibody Fab
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4

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Macromolecule #1: Envelope glycoprotein BG505 DS-SOSIP gp41

MacromoleculeName: Envelope glycoprotein BG505 DS-SOSIP gp41 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 17.162525 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString:
AVGIGAVFLG FLGAAGSTMG AASMTLTVQA RNLLSGIVQQ QSNLLRAIEA QQHLLKLTVW GIKQLQARVL AVERYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNRNLS EIWDNMTWLQ WDKEISNYTQ IIYGLLEESQ NQQEKNEQDL LALD

UniProtKB: Envelope glycoprotein gp160

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Macromolecule #2: Envelope glycoprotein BG505 DS-SOSIP gp120

MacromoleculeName: Envelope glycoprotein BG505 DS-SOSIP gp120 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 52.986969 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: AENLWVTVYY GVPVWKDAET TLFCASDAKA YETEKHNVWA THACVPTDPN PQEIHLENVT EEFNMWKNNM VEQMHTDIIS LWDQSLKPC VKLTPLCVTL QCTNVTNNIT DDMRGELKNC SFNMTTELRD KKQKVYSLFY RLDVVQINEN QGNRSNNSNK E YRLINCNT ...String:
AENLWVTVYY GVPVWKDAET TLFCASDAKA YETEKHNVWA THACVPTDPN PQEIHLENVT EEFNMWKNNM VEQMHTDIIS LWDQSLKPC VKLTPLCVTL QCTNVTNNIT DDMRGELKNC SFNMTTELRD KKQKVYSLFY RLDVVQINEN QGNRSNNSNK E YRLINCNT SACTQACPKV SFEPIPIHYC APAGFAILKC KDKKFNGTGP CPSVSTVQCT HGIKPVVSTQ LLLNGSLAEE EV MIRSENI TNNAKNILVQ FNTPVQINCT RPNNNTRKSI RIGPGQAFYA TGDIIGDIRQ AHCNVSKATW NETLGKVVKQ LRK HFGNNT IIRFANSSGG DLEVTTHSFN CGGEFFYCNT SGLFNSTWIS NTSVQGSNST GSNDSITLPC RIKQIINMWQ RIGQ CMYAP PIQGVIRCVS NITGLILTRD GGSTNSTTET FRPGGGDMRD NWRSELYKYK VVKIEPLGVA PTRCKRRV

UniProtKB: Envelope glycoprotein gp160

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Macromolecule #3: Fab 2C09 heavy chain

MacromoleculeName: Fab 2C09 heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.761762 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: EVQLVESGEG LVQPGGSLRL SCAASGFTFS SHAMHWVRQA PGKGLEYVSA ISSEGGSTYY ADSVRGRFII SRDNSKNTLY LQMGSLRAE DMAVYYCARV TGDYNWYFDL WGRGTLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS ...String:
EVQLVESGEG LVQPGGSLRL SCAASGFTFS SHAMHWVRQA PGKGLEYVSA ISSEGGSTYY ADSVRGRFII SRDNSKNTLY LQMGSLRAE DMAVYYCARV TGDYNWYFDL WGRGTLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKKV EPKSCDKGLE VLFQ

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Macromolecule #4: Fab 2C09 light chain

MacromoleculeName: Fab 2C09 light chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.281764 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: EIVMTQSPAT LSVSPGERAT LSCRASQGVS SNLAWYQQKP GQAPRLLIHG ASTRATGSPA RFSGSGSGTE FTLTISSLQS EDFAVYSCQ QYHNWPWTFG QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String:
EIVMTQSPAT LSVSPGERAT LSCRASQGVS SNLAWYQQKP GQAPRLLIHG ASTRATGSPA RFSGSGSGTE FTLTISSLQS EDFAVYSCQ QYHNWPWTFG QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC

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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: 15 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

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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: 7.4 / Details: PBS + 0.1mM DDM
GridModel: Quantifoil R2/2 / Material: GOLD / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec.
VitrificationCryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 58.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

6cdi

Initial angle assignmentType: NOT APPLICABLE / Software - Name: UCSF Chimera
Final 3D classificationSoftware - Name: cryoSPARC (ver. 3.3)
Final angle assignmentType: NOT APPLICABLE
Final reconstructionApplied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 2.81 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 3.3) / Number images used: 445733
FSC plot (resolution estimation)

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Atomic model buiding 1

RefinementProtocol: FLEXIBLE FIT
Output model

PDB-8g4t:
Vaccine-elicited human antibody 2C09 in complex with HIV-1 envelope trimer BG505 DS-SOSIP

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