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- EMDB-48283: 61-12A01 Fab in complex with HIV-1 GT1.1 v4.1 SOSIP Env trimer an... -
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Basic information
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Title | 61-12A01 Fab in complex with HIV-1 GT1.1 v4.1 SOSIP Env trimer and RM20A3 Fab | |||||||||
![]() | sharpened map | |||||||||
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![]() | HIV-1 / SOSIP / germline targeting / VRC01 / clinical trial / human / precursor antibody / VIRAL PROTEIN | |||||||||
Function / homology | ![]() 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 ...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 | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
![]() | Phulera S / Ozorowski G / Ward AB | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Precise targeting of HIV broadly neutralizing antibody precursors in humans. Authors: Tom G Caniels / Madhu Prabhakaran / Gabriel Ozorowski / Kellie J MacPhee / Weiwei Wu / Karlijn van der Straten / Sashank Agrawal / Ronald Derking / Emma I M M Reiss / Katrina Millard / ...Authors: Tom G Caniels / Madhu Prabhakaran / Gabriel Ozorowski / Kellie J MacPhee / Weiwei Wu / Karlijn van der Straten / Sashank Agrawal / Ronald Derking / Emma I M M Reiss / Katrina Millard / Martina Turroja / Aimee Desrosiers / Jeffrey Bethony / Elissa Malkin / Marinus H Liesdek / Annelou van der Veen / Michelle Klouwens / Jonne L Snitselaar / Joey H Bouhuijs / Rhianna Bronson / Jalen Jean-Baptiste / Suprabhath Gajjala / Zahra Rikhtegaran Tehrani / Alison Benner / Mukundhan Ramaswami / Michael O Duff / Yung-Wen Liu / Alicia H Sato / Ju Yeong Kim / Isabel J L Baken / Catarina Mendes Silva / Tom P L Bijl / Jacqueline van Rijswijk / Judith A Burger / Albert Cupo / Anila Yasmeen / Swastik Phulera / Wen-Hsin Lee / Kipchoge N Randall / Shiyu Zhang / Martin M Corcoran / Isabel Regadas / Alex C Sullivan / David M Brown / Jennifer A Bohl / Kelli M Greene / Hongmei Gao / Nicole L Yates / Sheetal Sawant / Jan M Prins / Neeltje A Kootstra / Stephen M Kaminsky / Burc Barin / Farhad Rahaman / Margaret Meller / Vince Philiponis / Dagna S Laufer / Angela Lombardo / Lindsey Mwoga / Solmaz Shotorbani / Drienna Holman / Richard A Koup / Per Johan Klasse / Gunilla B Karlsson Hedestam / Georgia D Tomaras / Marit J van Gils / David C Montefiori / Adrian B McDermott / Ollivier Hyrien / John P Moore / Ian A Wilson / Andrew B Ward / David J Diemert / Godelieve J de Bree / Sarah F Andrews / Marina Caskey / Rogier W Sanders / ![]() ![]() ![]() Abstract: A protective HIV vaccine will need to induce broadly neutralizing antibodies (bnAbs) in humans, but priming rare bnAb precursor B cells has been challenging. In a double-blinded, placebo-controlled ...A protective HIV vaccine will need to induce broadly neutralizing antibodies (bnAbs) in humans, but priming rare bnAb precursor B cells has been challenging. In a double-blinded, placebo-controlled phase 1 human clinical trial, the recombinant, germline-targeting envelope glycoprotein (Env) trimer BG505 SOSIP.v4.1-GT1.1, adjuvanted with AS01, induced bnAb precursors of the VRC01-class at a high frequency in the majority of vaccine recipients. These bnAb precursors, that target the CD4 receptor binding site, had undergone somatic hypermutation characteristic of the VRC01-class. A subset of isolated VRC01-class monoclonal antibodies neutralized wild-type pseudoviruses and was structurally extremely similar to bnAb VRC01. These results further support germline-targeting approaches for human HIV vaccine design and demonstrate atomic-level manipulation of B cell responses with rational vaccine design. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 230.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 29.3 KB 29.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 13.1 KB | Display | ![]() |
Images | ![]() | 100.2 KB | ||
Masks | ![]() | 244.1 MB | ![]() | |
Filedesc metadata | ![]() | 8.5 KB | ||
Others | ![]() ![]() | 226.4 MB 226.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 920.7 KB | Display | ![]() |
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Full document | ![]() | 920.3 KB | Display | |
Data in XML | ![]() | 22.3 KB | Display | |
Data in CIF | ![]() | 29 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9mi0MC ![]() 9miaC ![]() 9mibC ![]() 9micC ![]() 9midC ![]() 9mifC ![]() 9mihC ![]() 9miiC ![]() 9mj3C ![]() 9mj6C ![]() 9mjcC ![]() 9mjdC ![]() 9mjiC ![]() 9mk4C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | sharpened map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.0339 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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Density Histograms |
-Half map: half map A
File | emd_48283_half_map_1.map | ||||||||||||
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Annotation | half map A | ||||||||||||
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Density Histograms |
-Half map: half map B
File | emd_48283_half_map_2.map | ||||||||||||
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Annotation | half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : 61-12A01 Fab in complex with HIV-1 GT1.1 v4.1 SOSIP Env trimer an...
Entire | Name: 61-12A01 Fab in complex with HIV-1 GT1.1 v4.1 SOSIP Env trimer and RM20A3 Fab |
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Components |
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-Supramolecule #1: 61-12A01 Fab in complex with HIV-1 GT1.1 v4.1 SOSIP Env trimer an...
Supramolecule | Name: 61-12A01 Fab in complex with HIV-1 GT1.1 v4.1 SOSIP Env trimer and RM20A3 Fab type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: 61_12A01 heavy chain Fv
Macromolecule | Name: 61_12A01 heavy chain Fv / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 13.989641 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVQLVQSGAE VKQPGASVKV SCKASGYTFS DHFMHWVRQA PGQGLEWMGW INPKSGGPNY AQKFQGRVTM TRDRSISTAY MELRGLRSD DTAIYYCARP MHDYDDHDWY FDLWGRGTLV TVSS |
-Macromolecule #2: 61_12A01 kappa chain Fv
Macromolecule | Name: 61_12A01 kappa chain Fv / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 11.199423 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: VSVLTQSPGT LSLSPGERAT LSCRASQTVG SSYLAWYQQK PGQAPRLLIY GASSRATGIP DRFSGSGSGT DFTLTISRLE PEDFAVYYC QQYEAFGQGT KVEIK |
-Macromolecule #3: RM20A3 heavy chain Fv
Macromolecule | Name: RM20A3 heavy chain Fv / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 13.511111 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EVQLVETGGG LVQPGGSLKL SCRASGYTFS SFAMSWVRQA PGKGLEWVSL INDRGGLTFY VDSVKGRFTI SRDNSKNTLS LQMHSLRDG DTAVYYCATG GMSSALQSSK YYFDFWGQGA LVTVSS |
-Macromolecule #4: RM20A3 light chain Fv
Macromolecule | Name: RM20A3 light chain Fv / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 13.5088 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: ALTQPPSVSG SPGQSVTISC TGTSSDIGSY NYVSWYQQHP GKAPKLMIYD VTQRPSGVSD RFSGSKSGNT ASLTISGLQA DDEADYYCS AYAGRQTFYI FGGGTRLTVL GQPKASPTVT LFPPSSEEL |
-Macromolecule #5: GT1.1 v4.1 SOSIP gp120
Macromolecule | Name: GT1.1 v4.1 SOSIP gp120 / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 57.27548 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARAENLW VTVYYGVPVW KDAETTLFCA SDAKAYETKK HNVWATHACV PTDPNPQEI HLENVTEEFN MWKNNMVEQM HTDIISLWDQ SLKPCVKLTP LCVTLQCTNV TNNITDDMRG ELKNCSFNMT T ELRDKRQK ...String: MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARAENLW VTVYYGVPVW KDAETTLFCA SDAKAYETKK HNVWATHACV PTDPNPQEI HLENVTEEFN MWKNNMVEQM HTDIISLWDQ SLKPCVKLTP LCVTLQCTNV TNNITDDMRG ELKNCSFNMT T ELRDKRQK VHALFYKLDI VPINENQNTS YRLINCNTAA ITQACPKVSF EPIPIHYCAP AGFAILKCKD KKFNGTGPCP SV STVQCTH GIKPVVSTQL LLNGSLAEEE VMIRSKDIRN NAKNILVQFN TPVQINCTRP NNNTRKSIRI GPGQWFYATG DII GDIRQA HCNVSKATWN ETLGKVVKQL RKHFGNNTII RFANSSGGDL EVTTHSFNCG GEFFYCDTSG LFNSTWISNT SVQG SNSTG SNDSITLPCR IKQIINMWQR IGQAMYAPPI QGVIRCVSNI TGLILTRDGG STDSTTETFR PSGGDMRDNW RSELY KYKV VKIEPLGVAP TRCKRRVVGR RRRRR |
-Macromolecule #6: Envelope glycoprotein gp160
Macromolecule | Name: Envelope glycoprotein gp160 / type: protein_or_peptide / ID: 6 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 17.146482 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: AVGIGAVFLG FLGAAGSTMG AASMTLTVQA RNLLSGIVQQ QSNLLRAPEA QQHLLKLTVW GIKQLQARVL AVERYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNRNLS EIWDNMTWLQ WDKEISNYTQ IIYGLLEESQ NQQEKNEQDL LALD UniProtKB: Envelope glycoprotein gp160 |
-Macromolecule #9: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 9 / Number of copies: 24 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 2.1 mg/mL |
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Buffer | pH: 7.4 |
Grid | Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: TFS FALCON 4i (4k x 4k) / Number grids imaged: 1 / Number real images: 3867 / Average exposure time: 2.57 sec. / Average electron dose: 45.2 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 20.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.7000000000000001 µm / Nominal magnification: 190000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |