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Yorodumi- EMDB-28941: HIV Env BG505_MD39_B11 SOSIP boosting trimer in complex with B11_... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-28941 | |||||||||
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Title | HIV Env BG505_MD39_B11 SOSIP boosting trimer in complex with B11_d77.7 mouse Fab and RM20A3 Fab | |||||||||
Map data | sharpened map | |||||||||
Sample |
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Keywords | mouse antibody / germline targeting / HIV-1 / vaccine design / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Biological species | Human immunodeficiency virus / Macaca mulatta (Rhesus monkey) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.14 Å | |||||||||
Authors | Torres JL / Ozorowski G / Ward AB | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Science / Year: 2024 Title: mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies. Authors: Zhenfei Xie / Ying-Cing Lin / Jon M Steichen / Gabriel Ozorowski / Sven Kratochvil / Rashmi Ray / Jonathan L Torres / Alessia Liguori / Oleksandr Kalyuzhniy / Xuesong Wang / John E Warner / ...Authors: Zhenfei Xie / Ying-Cing Lin / Jon M Steichen / Gabriel Ozorowski / Sven Kratochvil / Rashmi Ray / Jonathan L Torres / Alessia Liguori / Oleksandr Kalyuzhniy / Xuesong Wang / John E Warner / Stephanie R Weldon / Gordon A Dale / Kathrin H Kirsch / Usha Nair / Sabyasachi Baboo / Erik Georgeson / Yumiko Adachi / Michael Kubitz / Abigail M Jackson / Sara T Richey / Reid M Volk / Jeong Hyun Lee / Jolene K Diedrich / Thavaleak Prum / Samantha Falcone / Sunny Himansu / Andrea Carfi / John R Yates / James C Paulson / Devin Sok / Andrew B Ward / William R Schief / Facundo D Batista / Abstract: Germline-targeting (GT) HIV vaccine strategies are predicated on deriving broadly neutralizing antibodies (bnAbs) through multiple boost immunogens. However, as the recruitment of memory B cells ...Germline-targeting (GT) HIV vaccine strategies are predicated on deriving broadly neutralizing antibodies (bnAbs) through multiple boost immunogens. However, as the recruitment of memory B cells (MBCs) to germinal centers (GCs) is inefficient and may be derailed by serum antibody-induced epitope masking, driving further B cell receptor (BCR) modification in GC-experienced B cells after boosting poses a challenge. Using humanized immunoglobulin knockin mice, we found that GT protein trimer immunogen N332-GT5 could prime inferred-germline precursors to the V3-glycan-targeted bnAb BG18 and that B cells primed by N332-GT5 were effectively boosted by either of two novel protein immunogens designed to have minimum cross-reactivity with the off-target V1-binding responses. The delivery of the prime and boost immunogens as messenger RNA lipid nanoparticles (mRNA-LNPs) generated long-lasting GCs, somatic hypermutation, and affinity maturation and may be an effective tool in HIV vaccine development. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_28941.map.gz | 259.7 MB | EMDB map data format | |
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Header (meta data) | emd-28941-v30.xml emd-28941.xml | 23.6 KB 23.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_28941_fsc.xml | 14.4 KB | Display | FSC data file |
Images | emd_28941.png | 71.9 KB | ||
Masks | emd_28941_msk_1.map | 274.6 MB | Mask map | |
Filedesc metadata | emd-28941.cif.gz | 7.4 KB | ||
Others | emd_28941_half_map_1.map.gz emd_28941_half_map_2.map.gz | 254.9 MB 254.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-28941 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-28941 | HTTPS FTP |
-Validation report
Summary document | emd_28941_validation.pdf.gz | 890.5 KB | Display | EMDB validaton report |
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Full document | emd_28941_full_validation.pdf.gz | 890.1 KB | Display | |
Data in XML | emd_28941_validation.xml.gz | 22.9 KB | Display | |
Data in CIF | emd_28941_validation.cif.gz | 29.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28941 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28941 | HTTPS FTP |
-Related structure data
Related structure data | 8f92MC 8f9gC 8f9mC 8vfvC 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_28941.map.gz / Format: CCP4 / Size: 274.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | sharpened map | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.15 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_28941_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: half map B
File | emd_28941_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_28941_half_map_2.map | ||||||||||||
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Annotation | half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : HIV-1 Env BG505_MD39_B11 SOSIP in complex with Fabs B11_d77.7 and...
Entire | Name: HIV-1 Env BG505_MD39_B11 SOSIP in complex with Fabs B11_d77.7 and RM20A3 |
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Components |
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-Supramolecule #1: HIV-1 Env BG505_MD39_B11 SOSIP in complex with Fabs B11_d77.7 and...
Supramolecule | Name: HIV-1 Env BG505_MD39_B11 SOSIP in complex with Fabs B11_d77.7 and RM20A3 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
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-Macromolecule #1: BG505_MD39_B11 gp120
Macromolecule | Name: BG505_MD39_B11 gp120 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Human immunodeficiency virus |
Molecular weight | Theoretical: 54.126512 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: AENLWVTVYY GVPVWKDAET TLFCASDAKA YETEKHNVWA THACVPTDPN PQEIHLENVT EEFNMWKNNM VEQMHEDIIS LWDQSLKPC VKLTPLCVTL QCTNYTPNLT SMMRGELKNC SFNMTTELRD KKQKVYSLFY RLDVVQINEN QGNRSNNSNK E YRLINCNT ...String: AENLWVTVYY GVPVWKDAET TLFCASDAKA YETEKHNVWA THACVPTDPN PQEIHLENVT EEFNMWKNNM VEQMHEDIIS LWDQSLKPC VKLTPLCVTL QCTNYTPNLT SMMRGELKNC SFNMTTELRD KKQKVYSLFY RLDVVQINEN QGNRSNNSNK E YRLINCNT SAITQACPKV SFEPIPIHYC APAGFAILKC KDKKFNGTGP CPSVSTVQCT HGIKPVVSTQ LLLNGSLAEE EV IIRSENI TNNAKNILVQ LNTPVQINCT RPNNNTVKSI RIGPGQAFYY TGDIIGDIRM AHCNVSKATW NETLGKVVKQ LRK HFGNNT IIRFAQSSGG DLEVTTHSFN CGGEFFYCNT SGLFNSTWIS NTSVQGSNST GSNDSITLPC RIKQIINMWQ RIGQ AMYAP PIQGVIRCVS NITGLILTRD GGSTNSTTET FRPGGGDMRD NWRSELYKYK VVKIEPLGVA PTRCKRRVVG RRRRR R |
-Macromolecule #2: RM20A3 Fab heavy chain
Macromolecule | Name: RM20A3 Fab heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Macaca mulatta (Rhesus monkey) |
Molecular weight | Theoretical: 13.511111 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLVETGGG LVQPGGSLKL SCRASGYTFS SFAMSWVRQA PGKGLEWVSL INDRGGLTFY VDSVKGRFTI SRDNSKNTLS LQMHSLRDG DTAVYYCATG GMSSALQSSK YYFDFWGQGA LVTVSS |
-Macromolecule #3: RM20A3 Fab light chain
Macromolecule | Name: RM20A3 Fab light chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Macaca mulatta (Rhesus monkey) |
Molecular weight | Theoretical: 13.5088 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: ALTQPPSVSG SPGQSVTISC TGTSSDIGSY NYVSWYQQHP GKAPKLMIYD VTQRPSGVSD RFSGSKSGNT ASLTISGLQA DDEADYYCS AYAGRQTFYI FGGGTRLTVL GQPKASPTVT LFPPSSEEL |
-Macromolecule #4: BG505_MD39_B11 gp41
Macromolecule | Name: BG505_MD39_B11 gp41 / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Human immunodeficiency virus |
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 |
-Macromolecule #5: B11_d77.7 Fab heavy chain
Macromolecule | Name: B11_d77.7 Fab heavy chain / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 14.061645 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLQESGPG LVQPSGTLSL TCAVSGDSIS SNNWWTWVRQ PPGKGLEWIG EIYQSGITKY NPSLKSRVST SVDKSKNQFS LRLSSVTAA DTAVYYCARS AISIFGVVVL GEYYYNGMDV WGQGTTVTVS S |
-Macromolecule #6: B11_d77.7 Fab kappa light chain
Macromolecule | Name: B11_d77.7 Fab kappa light chain / type: protein_or_peptide / ID: 6 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 11.76193 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIQMTQSPAS QSVSVGETVT ITCRVSENIY SHLAWYQQKQ GKSPQLLVYG ATNLADGVPS RFSGSGSGTQ YSLKINNLQS EDFGSYYCQ HFWDAPYTFG GGTKLEIK |
-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: 45 / 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 | 5.9 mg/mL |
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Buffer | pH: 7.4 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV / Details: 5-6 s blot time. |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average exposure time: 9.8 sec. / Average electron dose: 50.7 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.5 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |