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Yorodumi- EMDB-40825: 10E8-GT10.2 immunogen in complex with human Fab 10E8 and mouse Fa... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-40825 | |||||||||
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Title | 10E8-GT10.2 immunogen in complex with human Fab 10E8 and mouse Fab W6-10 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | HIV / Germline targeting / MPER / broadly neutralizing antibody / vaccine design / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Biological species | Mus musculus (house mouse) / synthetic construct (others) / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.0 Å | |||||||||
Authors | Huang J / Ozorowski G / Ward AB | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Nat Immunol / Year: 2024 Title: Vaccination induces broadly neutralizing antibody precursors to HIV gp41. Authors: Torben Schiffner / Ivy Phung / Rashmi Ray / Adriana Irimia / Ming Tian / Olivia Swanson / Jeong Hyun Lee / Chang-Chun D Lee / Ester Marina-Zárate / So Yeon Cho / Jiachen Huang / Gabriel ...Authors: Torben Schiffner / Ivy Phung / Rashmi Ray / Adriana Irimia / Ming Tian / Olivia Swanson / Jeong Hyun Lee / Chang-Chun D Lee / Ester Marina-Zárate / So Yeon Cho / Jiachen Huang / Gabriel Ozorowski / Patrick D Skog / Andreia M Serra / Kimmo Rantalainen / Joel D Allen / Sabyasachi Baboo / Oscar L Rodriguez / Sunny Himansu / Jianfu Zhou / Jonathan Hurtado / Claudia T Flynn / Katherine McKenney / Colin Havenar-Daughton / Swati Saha / Kaitlyn Shields / Steven Schulze / Melissa L Smith / Chi-Hui Liang / Laura Toy / Simone Pecetta / Ying-Cing Lin / Jordan R Willis / Fabian Sesterhenn / Daniel W Kulp / Xiaozhen Hu / Christopher A Cottrell / Xiaoya Zhou / Jennifer Ruiz / Xuesong Wang / Usha Nair / Kathrin H Kirsch / Hwei-Ling Cheng / Jillian Davis / Oleksandr Kalyuzhniy / Alessia Liguori / Jolene K Diedrich / Julia T Ngo / Vanessa Lewis / Nicole Phelps / Ryan D Tingle / Skye Spencer / Erik Georgeson / Yumiko Adachi / Michael Kubitz / Saman Eskandarzadeh / Marc A Elsliger / Rama R Amara / Elise Landais / Bryan Briney / Dennis R Burton / Diane G Carnathan / Guido Silvestri / Corey T Watson / John R Yates / James C Paulson / Max Crispin / Gevorg Grigoryan / Andrew B Ward / Devin Sok / Frederick W Alt / Ian A Wilson / Facundo D Batista / Shane Crotty / William R Schief / Abstract: A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design ...A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design of priming immunogens that induce rare bnAb-precursor B cells. The high neutralization breadth of the HIV bnAb 10E8 makes elicitation of 10E8-class bnAbs desirable; however, the recessed epitope within gp41 makes envelope trimers poor priming immunogens and requires that 10E8-class bnAbs possess a long heavy chain complementarity determining region 3 (HCDR3) with a specific binding motif. We developed germline-targeting epitope scaffolds with affinity for 10E8-class precursors and engineered nanoparticles for multivalent display. Scaffolds exhibited epitope structural mimicry and bound bnAb-precursor human naive B cells in ex vivo screens, protein nanoparticles induced bnAb-precursor responses in stringent mouse models and rhesus macaques, and mRNA-encoded nanoparticles triggered similar responses in mice. Thus, germline-targeting epitope scaffold nanoparticles can elicit rare bnAb-precursor B cells with predefined binding specificities and HCDR3 features. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_40825.map.gz | 259.3 MB | EMDB map data format | |
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Header (meta data) | emd-40825-v30.xml emd-40825.xml | 26.3 KB 26.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_40825_fsc.xml | 13.8 KB | Display | FSC data file |
Images | emd_40825.png | 45.3 KB | ||
Masks | emd_40825_msk_1.map | 274.6 MB | Mask map | |
Filedesc metadata | emd-40825.cif.gz | 7.6 KB | ||
Others | emd_40825_half_map_1.map.gz emd_40825_half_map_2.map.gz | 254.7 MB 254.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-40825 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40825 | HTTPS FTP |
-Related structure data
Related structure data | 8sx3MC 8tznC 8tzwC 8u03C 8u08C 8v2eC M: atomic model generated by this map C: citing same article (ref.) |
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-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_40825.map.gz / Format: CCP4 / Size: 274.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.725 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_40825_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_40825_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_40825_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : 10E8-GT10.2 immunogen in complex with human Fab 10E8 and mouse Fa...
Entire | Name: 10E8-GT10.2 immunogen in complex with human Fab 10E8 and mouse Fab W6-10 |
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Components |
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-Supramolecule #1: 10E8-GT10.2 immunogen in complex with human Fab 10E8 and mouse Fa...
Supramolecule | Name: 10E8-GT10.2 immunogen in complex with human Fab 10E8 and mouse Fab W6-10 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: W6-10 mouse Fab heavy chain, W6-10 mouse light chain
Supramolecule | Name: W6-10 mouse Fab heavy chain, W6-10 mouse light chain / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Supramolecule #3: 10E8-GT10.2 immunogen
Supramolecule | Name: 10E8-GT10.2 immunogen / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3 |
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Source (natural) | Organism: synthetic construct (others) |
-Supramolecule #4: 10E8 Fab heavy chain, 10E8 light chain
Supramolecule | Name: 10E8 Fab heavy chain, 10E8 light chain / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #4-#5 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: W6-10 mouse Fab heavy chain
Macromolecule | Name: W6-10 mouse Fab heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 23.97401 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVTLKESGPG ILQPSQTLSL TCSFSGFSLS TFGMGVGWIR QPSGKGLEWL AHIWWDDDKF YNPALKSRLT ISKDTSKNQV FLKIANVDT ADTATYYCAR IGEDYFLDVW GKGTTVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS W NSGALTSG ...String: QVTLKESGPG ILQPSQTLSL TCSFSGFSLS TFGMGVGWIR QPSGKGLEWL AHIWWDDDKF YNPALKSRLT ISKDTSKNQV FLKIANVDT ADTATYYCAR IGEDYFLDVW GKGTTVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS W NSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKKVE PKSCDK |
-Macromolecule #2: W6-10 mouse light chain
Macromolecule | Name: W6-10 mouse light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 23.417891 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIQMTQSPAS LSASVGETVT ITCRASGNIH NYLAWYQQKQ GKSPQLLVYN AKTLADGVPS RFSGSGSGTQ YSLKINSLQP EDFGSYYCQ HFWSAPYTFG GGTNLEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String: DIQMTQSPAS LSASVGETVT ITCRASGNIH NYLAWYQQKQ GKSPQLLVYN AKTLADGVPS RFSGSGSGTQ YSLKINSLQP EDFGSYYCQ HFWSAPYTFG GGTNLEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC |
-Macromolecule #3: 10E8-GT10.2 immunogen
Macromolecule | Name: 10E8-GT10.2 immunogen / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 21.07375 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: TGNVTQEDII RALASPLIKD GMVDEDFAEY VIARENRSPT GLQAKGVGVA IPHTLGDYVR DNAISVGILD KPVNFSGWYQ SPDPVPVRV VFMLAGRTWD DIVIVLKWIK DVILDEEFMK RLLNMSDEEI YRQIYTRISK APNLSGINFS REYVRHLNGS G GSGLNDIF EAQKIEWHEG SGGHHHHHH |
-Macromolecule #4: 10E8 Fab heavy chain
Macromolecule | Name: 10E8 Fab heavy chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 25.175193 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLVESGGG LVKPGGSLRL SCSASGFDFD NAWMTWVRQP PGKGLEWVGR ITGPGEGWSV DYAAPVEGRF TISRLNSINF LYLEMNNLR MEDSGLYFCA RTGKYYDFWS GYPPGEEYFQ DWGRGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL V KDYFPEPV ...String: EVQLVESGGG LVKPGGSLRL SCSASGFDFD NAWMTWVRQP PGKGLEWVGR ITGPGEGWSV DYAAPVEGRF TISRLNSINF LYLEMNNLR MEDSGLYFCA RTGKYYDFWS GYPPGEEYFQ DWGRGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL V KDYFPEPV TVSWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKK VEPKSC |
-Macromolecule #5: 10E8 light chain
Macromolecule | Name: 10E8 light chain / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 22.959434 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: SYELTQETGV SVALGRTVTI TCRGDSLRSH YASWYQKKPG QAPILLFYGK NNRPSGVPDR FSGSASGNRA SLTISGAQAE DDAEYYCSS RDKSGSRLSV FGGGTKLTVL GQPKAAPSVT LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK A GVETTTPS ...String: SYELTQETGV SVALGRTVTI TCRGDSLRSH YASWYQKKPG QAPILLFYGK NNRPSGVPDR FSGSASGNRA SLTISGAQAE DDAEYYCSS RDKSGSRLSV FGGGTKLTVL GQPKAAPSVT LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK A GVETTTPS KQSNNKYAAS SYLSLTPEQW KSHRSYSCQV THEGSTVEKT VAPTECS |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 2.5 mg/mL | ||||||||
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Buffer | pH: 7.4 Component:
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Grid | Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 200 / 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 |
-Electron microscopy
Microscope | TFS GLACIOS |
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Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.7000000000000001 µm |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 53.0 e/Å2 |