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Yorodumi- EMDB-7876: BG505 MD64 N332-GT2 SOSIP trimer in complex with germline-reverte... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-7876 | ||||||||||||
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Title | BG505 MD64 N332-GT2 SOSIP trimer in complex with germline-reverted BG18 fragment antigen binding | ||||||||||||
Map data | Sharpened map | ||||||||||||
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 / 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 / structural molecule activity / virion attachment to host cell / host cell plasma membrane / 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: 3.85 Å | ||||||||||||
Authors | Ozorowski G / Steichen JM / Schief WR / Ward AB | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: Science / Year: 2019 Title: A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses. Authors: Jon M Steichen / Ying-Cing Lin / Colin Havenar-Daughton / Simone Pecetta / Gabriel Ozorowski / Jordan R Willis / Laura Toy / Devin Sok / Alessia Liguori / Sven Kratochvil / Jonathan L Torres ...Authors: Jon M Steichen / Ying-Cing Lin / Colin Havenar-Daughton / Simone Pecetta / Gabriel Ozorowski / Jordan R Willis / Laura Toy / Devin Sok / Alessia Liguori / Sven Kratochvil / Jonathan L Torres / Oleksandr Kalyuzhniy / Eleonora Melzi / Daniel W Kulp / Sebastian Raemisch / Xiaozhen Hu / Steffen M Bernard / Erik Georgeson / Nicole Phelps / Yumiko Adachi / Michael Kubitz / Elise Landais / Jeffrey Umotoy / Amanda Robinson / Bryan Briney / Ian A Wilson / Dennis R Burton / Andrew B Ward / Shane Crotty / Facundo D Batista / William R Schief / Abstract: Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for ...Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity-determining region 3 (HCDR3) is a major barrier. Exploiting ultradeep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer-based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model and bound a range of potential bnAb-precursor human naïve B cells in ex vivo screens. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs and could be applied to most HCDR3-dominant antibodies from other pathogens. | ||||||||||||
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_7876.map.gz | 84.4 MB | EMDB map data format | |
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Header (meta data) | emd-7876-v30.xml emd-7876.xml | 26.1 KB 26.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_7876_fsc.xml | 10.2 KB | Display | FSC data file |
Images | emd_7876.png | 60.3 KB | ||
Masks | emd_7876_msk_1.map | 91.1 MB | Mask map | |
Others | emd_7876_half_map_1.map.gz emd_7876_half_map_2.map.gz | 71.3 MB 71.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-7876 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-7876 | HTTPS FTP |
-Related structure data
Related structure data | 6dfhMC 7875C 7884C 7885C 6dfgC 6nf5C 6nfcC 6oc7C C: citing same article (ref.) M: atomic model generated by this map |
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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_7876.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Sharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.03 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_7876_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: Half map 1
File | emd_7876_half_map_1.map | ||||||||||||
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Annotation | Half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 2
File | emd_7876_half_map_2.map | ||||||||||||
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Annotation | Half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : BG505 MD64 N332-GT2 SOSIP trimer in complex with germline-reverte...
Entire | Name: BG505 MD64 N332-GT2 SOSIP trimer in complex with germline-reverted BG18 fragment antigen binding |
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Components |
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-Supramolecule #1: BG505 MD64 N332-GT2 SOSIP trimer in complex with germline-reverte...
Supramolecule | Name: BG505 MD64 N332-GT2 SOSIP trimer in complex with germline-reverted BG18 fragment antigen binding type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Molecular weight | Theoretical: 570 KDa |
-Supramolecule #2: SOSIP trimer
Supramolecule | Name: SOSIP 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) |
-Supramolecule #3: BG18 fragment antigen
Supramolecule | Name: BG18 fragment antigen / 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) |
-Macromolecule #1: Envelope glycoprotein gp160
Macromolecule | Name: Envelope glycoprotein gp160 / 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: 53.497836 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: AENLWVTVYY GVPVWKDAET TLFCASDAKA YETEKHNVWA THECVPTDPN PQEIHLENVT EEFNMWKNNM VEQMHTDIIE LWDQSLKPC VKLTPLCVTL QCTNYAPKLR SMMRGEIKNC SFNMTTELRD KKQKVYSLFY RLDVVQINEN QGNRSNNSNK E YRLINCNT ...String: AENLWVTVYY GVPVWKDAET TLFCASDAKA YETEKHNVWA THECVPTDPN PQEIHLENVT EEFNMWKNNM VEQMHTDIIE LWDQSLKPC VKLTPLCVTL QCTNYAPKLR SMMRGEIKNC SFNMTTELRD KKQKVYSLFY RLDVVQINEN QGNRSNNSNK E YRLINCNT SAITQACPKV SFEPIPIHYC APAGFAILKC KDKKFNGTGP CPSVSTVQCT HGIKPVVSTQ LLLNGSLAEE EV IIRSENI TNNAKNILVQ LNTPVQINCT RPNNNTVKSI RIGPGQAFYY FGDVLGDVRM AHCNISKATW NETLGKVVKQ LRK HFGNNT IIRFAQSSGG DLEVTTHSFN CGGEFFYCNT SGLFNSTWIS NTSVQGSNST GSNDSLILPC RIKQIINMWQ RIGQ AMYAP PIQGVIRCVS NITGLILTRD GGSTNSTTET FRPGGGDMRD NWRSELYKYK VVKIEPLGVA PTRCKRRVVG R |
-Macromolecule #2: Envelope glycoprotein gp160
Macromolecule | Name: Envelope glycoprotein gp160 / 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: 18.209594 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: AVGIGAVSLG FLGAAGSTMG AASMTLTVQA RNLLSGIVQQ QSNLLRAPEP QQHLLKLTVW GIKQLQARVL AVEHYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNRNLS EIWDNMTWLQ WDKEISNYTQ IIYGLLEESQ NQQEKNEQDL LALDGTKHHH H HH |
-Macromolecule #3: germline-reverted BG18 fragment antigen binding heavy chain
Macromolecule | Name: germline-reverted BG18 fragment antigen binding 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: 24.602631 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLQESGPG LVKPSGTLSL TCAVSGGSIS SSNWWSWVRQ PPGKGLEWIG EIYHSGSTNY NPSLKSRVTI SVDKSKNQFS LKLSSVTAA DTAVYYCARN AITIFGVVII GEYYYYGMDV WGQGTTVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV K DYFPEPVT ...String: QVQLQESGPG LVKPSGTLSL TCAVSGGSIS SSNWWSWVRQ PPGKGLEWIG EIYHSGSTNY NPSLKSRVTI SVDKSKNQFS LKLSSVTAA DTAVYYCARN AITIFGVVII GEYYYYGMDV WGQGTTVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV K DYFPEPVT VSWNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKKV EPKSC |
-Macromolecule #4: germline-reverted BG18 fragment antigen binding light chain
Macromolecule | Name: germline-reverted BG18 fragment antigen binding 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: 22.861195 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: SYELTQPPSV SVSPGQTARI TCSGDALPKQ YAYWYQQKPG QAPVLVIYKD SERPSGIPER FSGSSSGTTV TLTISGVQAE DEADYYCQS ADSSGTYWVF GGGTKLTVLG QPKAAPSVTL FPPSSEELQA NKATLVCLIS DFYPGAVTVA WKADSSPVKA G VETTTPSK ...String: SYELTQPPSV SVSPGQTARI TCSGDALPKQ YAYWYQQKPG QAPVLVIYKD SERPSGIPER FSGSSSGTTV TLTISGVQAE DEADYYCQS ADSSGTYWVF GGGTKLTVLG QPKAAPSVTL FPPSSEELQA NKATLVCLIS DFYPGAVTVA WKADSSPVKA G VETTTPSK QSNNKYAASS YLSLTPEQWK SHRSYSCQVT HEGSTVEKTV APTECS |
-Macromolecule #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 8 / Number of copies: 18 / 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 | 4.2 mg/mL | ||||||||||||
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Buffer | pH: 7.4 Component:
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Grid | Model: C-flat-2/2 4C / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Atmosphere: OTHER / Details: Gatan Model 950 Advanced Plasma System | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 283 K / Instrument: FEI VITROBOT MARK IV / Details: 5 second blot time. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 29000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 3710 pixel / Digitization - Dimensions - Height: 3838 pixel / Number real images: 1031 / Average exposure time: 10.0 sec. / Average electron dose: 65.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: RIGID BODY FIT |
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Output model | PDB-6dfh: |