+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-41034 | |||||||||
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Title | MD64 N332-GT5 SOSIP | |||||||||
Map data | sharpened map | |||||||||
Sample |
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Keywords | germline targeting / SOSIP / Env / HIV / BG18 / immunogen design / VIRAL PROTEIN | |||||||||
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 / plasma membrane Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.6 Å | |||||||||
Authors | Ozorowski G / Torres JL / Ward AB | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Science / Year: 2024 Title: Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates. Authors: Jon M Steichen / Ivy Phung / Eugenia Salcedo / Gabriel Ozorowski / Jordan R Willis / Sabyasachi Baboo / Alessia Liguori / Christopher A Cottrell / Jonathan L Torres / Patrick J Madden / ...Authors: Jon M Steichen / Ivy Phung / Eugenia Salcedo / Gabriel Ozorowski / Jordan R Willis / Sabyasachi Baboo / Alessia Liguori / Christopher A Cottrell / Jonathan L Torres / Patrick J Madden / Krystal M Ma / Henry J Sutton / Jeong Hyun Lee / Oleksandr Kalyuzhniy / Joel D Allen / Oscar L Rodriguez / Yumiko Adachi / Tina-Marie Mullen / Erik Georgeson / Michael Kubitz / Alison Burns / Shawn Barman / Rohini Mopuri / Amanda Metz / Tasha K Altheide / Jolene K Diedrich / Swati Saha / Kaitlyn Shields / Steven E Schultze / Melissa L Smith / Torben Schiffner / Dennis R Burton / Corey T Watson / Steven E Bosinger / Max Crispin / John R Yates / James C Paulson / Andrew B Ward / Devin Sok / Shane Crotty / William R Schief / Abstract: Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically ...Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight rhesus macaques to substantial frequencies and with diverse lineages in germinal center and memory B cells. We confirmed bnAb-mimicking, HCDR3-dominant, trimer-binding interactions with cryo-electron microscopy. Our results demonstrate proof of principle for HCDR3-dominant bnAb-precursor priming in outbred animals and suggest that N332-GT5 holds promise for the induction of similar responses in humans. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_41034.map.gz | 324 MB | EMDB map data format | |
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Header (meta data) | emd-41034-v30.xml emd-41034.xml | 19.6 KB 19.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_41034_fsc.xml | 16.7 KB | Display | FSC data file |
Images | emd_41034.png | 118 KB | ||
Masks | emd_41034_msk_1.map | 343 MB | Mask map | |
Filedesc metadata | emd-41034.cif.gz | 6.8 KB | ||
Others | emd_41034_half_map_1.map.gz emd_41034_half_map_2.map.gz | 318.1 MB 318.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-41034 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41034 | HTTPS FTP |
-Validation report
Summary document | emd_41034_validation.pdf.gz | 914.2 KB | Display | EMDB validaton report |
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Full document | emd_41034_full_validation.pdf.gz | 913.7 KB | Display | |
Data in XML | emd_41034_validation.xml.gz | 24.2 KB | Display | |
Data in CIF | emd_41034_validation.cif.gz | 31.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41034 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41034 | HTTPS FTP |
-Related structure data
Related structure data | 8t4kMC 8t49C 8t4aC 8t4bC 8t4dC 8t4lC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_41034.map.gz / Format: CCP4 / Size: 343 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | sharpened map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.8015 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_41034_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: half map B
File | emd_41034_half_map_1.map | ||||||||||||
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Annotation | half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map A
File | emd_41034_half_map_2.map | ||||||||||||
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Annotation | half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : MD64 N332-GT5 SOSIP
Entire | Name: MD64 N332-GT5 SOSIP |
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Components |
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-Supramolecule #1: MD64 N332-GT5 SOSIP
Supramolecule | Name: MD64 N332-GT5 SOSIP / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
-Macromolecule #1: MD64 N332-GT5 SOSIP gp120
Macromolecule | Name: MD64 N332-GT5 SOSIP gp120 / 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: 54.236801 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: AENLWVTVYY GVPVWKDAET TLFCASDAKA YETEKHNVWA THACVPTDPN PQEIHLENVT EEFNMWKNNM VEQMHEDIIS LWDQSLKPC VKLTPLCVTL QCTNYAPKLR SMMRGEIKNC SFNMTTELRD KKQKVYSLFY RLDVVQINEN QGNRSNNSNK E YRLINCNT ...String: AENLWVTVYY GVPVWKDAET TLFCASDAKA YETEKHNVWA THACVPTDPN PQEIHLENVT EEFNMWKNNM VEQMHEDIIS LWDQSLKPC VKLTPLCVTL QCTNYAPKLR SMMRGEIKNC SFNMTTELRD KKQKVYSLFY RLDVVQINEN QGNRSNNSNK E YRLINCNT SAITQACPKV SFEPIPIHYC APAGFAILKC KDKKFNGTGP CPSVSTVQCT HGIKPVVSTQ LLLNGSLAEE EV IIRSENI TNNAKNILVQ LNTPVQINCT RPSNNTVKSI RIGPGQAFYY FGDVLGHVRM AHCNISKATW NETLGKVVKQ LRK HFGNNT IIRFAQSSGG DLEVTTHSFN CGGEFFYCNT SGLFNSTWIS NTSVQGSNST GSNDSLILPC WIKQIINMWQ RIGQ AMYAP PIQGVIRCVS NITGLILTRD GGSTNSTTET FRPGGGDMRD NWRSELYKYK VVKIEPLGVA PTRCKRRVVG RRRRR R |
-Macromolecule #2: MD64 N332-GT5 SOSIP gp41
Macromolecule | Name: MD64 N332-GT5 SOSIP gp41 / 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: 18.250541 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: AVGIGAVSLG FLGAAGSTMG AASMTLTVQA RNLLSGIVQQ QSNLLRAPEP QQHLLKDTHW GIKQLQARVL AVEHYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNRNLS EIWDNMTWLQ WDKEISNYTQ IIYGLLEESQ NQQEKNEQDL LALDGTKHHH H HH UniProtKB: Envelope glycoprotein gp160 |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 33 / 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 | 2.6 mg/mL |
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Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Detector mode: COUNTING / Average electron dose: 79.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 36000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |