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Yorodumi- EMDB-20175: Modified BG505 SOSIP-based immunogen RC1 in complex with the elic... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20175 | |||||||||
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Title | Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch bNAb 10-1074 | |||||||||
Map data | ||||||||||
Sample |
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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 / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / 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 / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / apoptotic process / host cell plasma membrane / structural molecule activity / virion membrane / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.05 Å | |||||||||
Authors | Abernathy ME / Gristick HB / Bjorkman PJ | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Nature / Year: 2019 Title: Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques. Authors: Amelia Escolano / Harry B Gristick / Morgan E Abernathy / Julia Merkenschlager / Rajeev Gautam / Thiago Y Oliveira / Joy Pai / Anthony P West / Christopher O Barnes / Alexander A Cohen / ...Authors: Amelia Escolano / Harry B Gristick / Morgan E Abernathy / Julia Merkenschlager / Rajeev Gautam / Thiago Y Oliveira / Joy Pai / Anthony P West / Christopher O Barnes / Alexander A Cohen / Haoqing Wang / Jovana Golijanin / Daniel Yost / Jennifer R Keeffe / Zijun Wang / Peng Zhao / Kai-Hui Yao / Jens Bauer / Lilian Nogueira / Han Gao / Alisa V Voll / David C Montefiori / Michael S Seaman / Anna Gazumyan / Murillo Silva / Andrew T McGuire / Leonidas Stamatatos / Darrell J Irvine / Lance Wells / Malcolm A Martin / Pamela J Bjorkman / Michel C Nussenzweig / Abstract: Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it ...Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_20175.map.gz | 28.7 MB | EMDB map data format | |
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Header (meta data) | emd-20175-v30.xml emd-20175.xml | 28.4 KB 28.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_20175_fsc.xml | 9.7 KB | Display | FSC data file |
Images | emd_20175.png | 78.6 KB | ||
Masks | emd_20175_msk_1.map | 34.3 MB | Mask map | |
Others | emd_20175_additional.map.gz emd_20175_half_map_1.map.gz emd_20175_half_map_2.map.gz | 32.1 MB 26.1 MB 28.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20175 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20175 | HTTPS FTP |
-Validation report
Summary document | emd_20175_validation.pdf.gz | 712.4 KB | Display | EMDB validaton report |
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Full document | emd_20175_full_validation.pdf.gz | 712 KB | Display | |
Data in XML | emd_20175_validation.xml.gz | 15.1 KB | Display | |
Data in CIF | emd_20175_validation.cif.gz | 19.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20175 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20175 | HTTPS FTP |
-Related structure data
Related structure data | 6ornMC 6oroC 6orpC 6orqC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_20175.map.gz / Format: CCP4 / Size: 34.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.436 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_20175_msk_1.map | ||||||||||||
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Density Histograms |
-Additional map: #1
File | emd_20175_additional.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_20175_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_20175_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Complex of RC1 variant of BG505 SOSIP.664 trimer with three 10-10...
Entire | Name: Complex of RC1 variant of BG505 SOSIP.664 trimer with three 10-1074 Fabs and three CD4bs Fabs |
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Components |
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-Supramolecule #1: Complex of RC1 variant of BG505 SOSIP.664 trimer with three 10-10...
Supramolecule | Name: Complex of RC1 variant of BG505 SOSIP.664 trimer with three 10-1074 Fabs and three CD4bs Fabs type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 Details: Fab fragments generated by recombinant expression and complexed with the RC1 variant of BG505 SOSIP.664 trimer |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Molecular weight | Theoretical: 600 KDa |
-Supramolecule #2: RC1 variant of BG505 SOSIP.664 trimer
Supramolecule | Name: RC1 variant of BG505 SOSIP.664 trimer / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: Expi293 |
-Supramolecule #3: 10-1074 Fab
Supramolecule | Name: 10-1074 Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#4 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: Expi293 |
-Macromolecule #1: RC1 variant of HIV-1 Env glycoprotein gp41
Macromolecule | Name: RC1 variant of HIV-1 Env glycoprotein gp41 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Molecular weight | Theoretical: 17.134324 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: AVGIGAVSLG FLGAAGSTMG AASMTLTVQA RNLLSGIVQQ QSNLLRAPEP QQHLLKDTHW GIKQLQARVL AVEHYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNRNLS EIWDNMTWLQ WDKEISNYTQ IIYGLLEESQ NQQEKNEQDL LALD |
-Macromolecule #2: RC1 variant of HIV-1 Env glycoprotein gp120
Macromolecule | Name: RC1 variant of HIV-1 Env glycoprotein gp120 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Molecular weight | Theoretical: 54.149566 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: AENLWVTVYY GVPVWKDAET TLFCASDAKA YETEKHNVWA THACVPTDPN PQEIHLENVT EEFNMWKNNM VEQMHEDIIS LWDQSLKPC VKLTPLCVTL QCTNYAPNLL SNMRGELKQC SFNMTTELRD KKQKVYSLFY RLDVVQINEN QGNRSNNSNK E YRLINCNT ...String: AENLWVTVYY 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 |
-Macromolecule #3: 10-1074 antibody Fab heavy chain
Macromolecule | Name: 10-1074 antibody Fab heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 25.661688 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLQESGPG LVKPSETLSV TCSVSGDSMN NYYWTWIRQS PGKGLEWIGY ISDRESATYN PSLNSRVVIS RDTSKNQLSL KLNSVTPAD TAVYYCATAR RGQRIYGVVS FGEFFYYYSM DVWGKGTTVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC L VKDYFPEP ...String: QVQLQESGPG LVKPSETLSV TCSVSGDSMN NYYWTWIRQS PGKGLEWIGY ISDRESATYN PSLNSRVVIS RDTSKNQLSL KLNSVTPAD TAVYYCATAR RGQRIYGVVS FGEFFYYYSM DVWGKGTTVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC L VKDYFPEP VTVSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK RVEPKSCDKT |
-Macromolecule #4: 10-1074 antibody Fab light chain
Macromolecule | Name: 10-1074 antibody Fab light chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.18076 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: SYVRPLSVAL GETARISCGR QALGSRAVQW YQHRPGQAPI LLIYNNQDRP SGIPERFSGT PDINFGTRAT LTISGVEAGD EADYYCHMW DSRSGFSWSF GGATRLTVLG QPKAAPSVTL FPPSSEELQA NKATLVCLIS DFYPGAVTVA WKADSSPVKA G VETTTPSK ...String: SYVRPLSVAL GETARISCGR QALGSRAVQW YQHRPGQAPI LLIYNNQDRP SGIPERFSGT PDINFGTRAT LTISGVEAGD EADYYCHMW DSRSGFSWSF GGATRLTVLG QPKAAPSVTL FPPSSEELQA NKATLVCLIS DFYPGAVTVA WKADSSPVKA G VETTTPSK QSNNKYAASS YLSLTPEQWK SHRSYSCQVT HEGSTVEKTV APTECS |
-Macromolecule #10: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 10 / Number of copies: 30 / 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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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.75 mg/mL | |||||||||
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Buffer | pH: 8 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV Details: 0 blot force, 3.5 second blot time, 3 uL sample added to freshly glow-discharged grids. |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Digitization - Frames/image: 1-40 / Number grids imaged: 1 / Number real images: 684 / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.4 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 73000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |