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- EMDB-41715: Lassa GPC (strain Josiah) bound to rabbit polyclonal fusion-pepti... -
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Open data
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Basic information
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Title | Lassa GPC (strain Josiah) bound to rabbit polyclonal fusion-peptide-targeting antibody FP-1 | |||||||||||||||
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![]() | Lassa virus glycoprotein complex / GPC / immune complex / antibody / polyclonal antibody / base antibody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||
Function / homology | ![]() host cell Golgi membrane / receptor-mediated endocytosis of virus by host cell / lyase activity / host cell endoplasmic reticulum membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / membrane / metal ion binding Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||||||||
![]() | Perrett HR / Brouwer PJM / Ward AB | |||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Defining bottlenecks and opportunities for Lassa virus neutralization by structural profiling of vaccine-induced polyclonal antibody responses. Authors: Philip J M Brouwer / Hailee R Perrett / Tim Beaumont / Haye Nijhuis / Sabine Kruijer / Judith A Burger / Ilja Bontjer / Wen-Hsin Lee / James A Ferguson / Martin Schauflinger / Helena Müller- ...Authors: Philip J M Brouwer / Hailee R Perrett / Tim Beaumont / Haye Nijhuis / Sabine Kruijer / Judith A Burger / Ilja Bontjer / Wen-Hsin Lee / James A Ferguson / Martin Schauflinger / Helena Müller-Kräuter / Rogier W Sanders / Thomas Strecker / Marit J van Gils / Andrew B Ward / ![]() ![]() ![]() Abstract: Lassa fever continues to be a major public health burden in West Africa, yet effective therapies or vaccines are lacking. The isolation of protective neutralizing antibodies against the Lassa virus ...Lassa fever continues to be a major public health burden in West Africa, yet effective therapies or vaccines are lacking. The isolation of protective neutralizing antibodies against the Lassa virus glycoprotein complex (GPC) justifies the development of vaccines that can elicit strong neutralizing antibody responses. However, Lassa vaccine candidates have generally been unsuccessful at doing so, and the associated antibody responses to these vaccines remain poorly characterized. Here, we establish an electron microscopy-based epitope mapping workflow that enables high-resolution structural characterization of polyclonal antibodies to the GPC. By applying this method to rabbits vaccinated with a recombinant GPC vaccine and a GPC-derived virus-like particle, we reveal determinants of neutralization that involve epitopes of the GPC-A competition cluster. Furthermore, by identifying undescribed immunogenic off-target epitopes, we expose the challenges that recombinant GPC vaccines face. By enabling detailed polyclonal antibody characterization, our work ushers in a next generation of more rational Lassa vaccine design. | |||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 450.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 23.9 KB 23.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 16.6 KB | Display | ![]() |
Images | ![]() | 98.9 KB | ||
Masks | ![]() | 476.8 MB | ![]() | |
Filedesc metadata | ![]() | 7 KB | ||
Others | ![]() ![]() ![]() | 59.5 MB 443.1 MB 443.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 25.7 KB | Display | |
Data in CIF | ![]() | 33.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8tyeMC ![]() 8tycC ![]() 8vcvC ![]() 8ve8C ![]() 9cj7C ![]() 9cj8C ![]() 9ck7C ![]() 9ck8C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
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
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-Additional map: #1
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-Half map: #2
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Density Histograms |
-Half map: #1
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Density Histograms |
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Sample components
-Entire : Heterotrimeric Lassa GPC bound to heterodimeric rabbit polyclonal...
Entire | Name: Heterotrimeric Lassa GPC bound to heterodimeric rabbit polyclonal fusion-peptide-targeting antibody FP-1 |
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Components |
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-Supramolecule #1: Heterotrimeric Lassa GPC bound to heterodimeric rabbit polyclonal...
Supramolecule | Name: Heterotrimeric Lassa GPC bound to heterodimeric rabbit polyclonal fusion-peptide-targeting antibody FP-1 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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-Supramolecule #2: Glycoprotein G1, Glycoprotein G2, 2-dehydro-3-deoxyphosphoglucona...
Supramolecule | Name: Glycoprotein G1, Glycoprotein G2, 2-dehydro-3-deoxyphosphogluconate aldolase/4-hydroxy-2-oxoglutarate aldolase fusion protein type: complex / ID: 2 / Parent: 1 / Macromolecule list: #3-#4 |
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Source (natural) | Organism: ![]() |
-Supramolecule #3: Polyclonal antibody FP-1 heavy chain, Polyclonal antibody FP-1 li...
Supramolecule | Name: Polyclonal antibody FP-1 heavy chain, Polyclonal antibody FP-1 light chain type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Polyclonal Fv heavy chain
Macromolecule | Name: Polyclonal Fv heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 9.890183 KDa |
Sequence | String: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK) ...String: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK) (UNK)(UNK)(UNK) |
-Macromolecule #2: Polyclonal Fv light chain
Macromolecule | Name: Polyclonal Fv light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 8.698714 KDa |
Sequence | String: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK) ...String: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) |
-Macromolecule #3: Glycoprotein GP1
Macromolecule | Name: Glycoprotein GP1 / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() Strain: Mouse/Sierra Leone/Josiah/1976 |
Molecular weight | Theoretical: 29.010352 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MGQIVTFFQE VPHVIEEVMN IVLIALSVLA VLKGLYNFAT CGLVGLVTFL LLCGRSCTTS LYKGVYELQT LELNMETLNM TMPLSCTKN NSHHYIMVGN ETGLELTLTN TSIINHKFCN LSDAHKKNLY DHALMSIIST FHLSIPNFNQ YEAMSCDFNG G KISVQYNL ...String: MGQIVTFFQE VPHVIEEVMN IVLIALSVLA VLKGLYNFAT CGLVGLVTFL LLCGRSCTTS LYKGVYELQT LELNMETLNM TMPLSCTKN NSHHYIMVGN ETGLELTLTN TSIINHKFCN LSDAHKKNLY DHALMSIIST FHLSIPNFNQ YEAMSCDFNG G KISVQYNL SHSYAGDAAN HCGTVANGVL QTFMRMAWGG SYIALDSGCG NWDCIMTSYQ YLIIQNTTWE DHCQFSRPSP IG YLGLLSQ RTRDIYISRR LL UniProtKB: Pre-glycoprotein polyprotein GP complex |
-Macromolecule #4: Glycoprotein GP2
Macromolecule | Name: Glycoprotein GP2 / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() Strain: ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8 |
Molecular weight | Theoretical: 44.765047 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GTFTWTLSDS EGKDTPGGYC LTRWMLIEAE LKCFGNTAVA KCNEKHDEEF CDMLRLFDFN KQAIQRLKAP AQMSIQLINK AVNALINDQ LIMKNHLRDI MCIPYCNYSK YWYLNHTTTG RTSLPKCWLV SNGSYLNETH FSDDIEQQAD NMITEMLQKE Y MERQGGSG ...String: GTFTWTLSDS EGKDTPGGYC LTRWMLIEAE LKCFGNTAVA KCNEKHDEEF CDMLRLFDFN KQAIQRLKAP AQMSIQLINK AVNALINDQ LIMKNHLRDI MCIPYCNYSK YWYLNHTTTG RTSLPKCWLV SNGSYLNETH FSDDIEQQAD NMITEMLQKE Y MERQGGSG GSGGSGGSGG SEKAAKAEEA ARKMEELFKK HKIVAVLRAN SVEEAIEKAV AVFAGGVHLI EITFTVPDAD TV IKALSVL KEKGAIIGAG TVTSVEQCRK AVESGAEFIV SPHLDEEISQ FCKEKGVFYM PGVMTPTELV KAMKLGHDIL KLF PGEVVG PEFVKAMKGP FPNVKFVPTG GVDLDNVCEW FDAGVLAVGV GDALVEGDPD EVREKAKEFV EKIRGCTEGS LEWS HPQFE K UniProtKB: Pre-glycoprotein polyprotein GP complex, 2-dehydro-3-deoxyphosphogluconate aldolase/4-hydroxy-2-oxoglutarate aldolase |
-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: 14 / 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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.1 mg/mL |
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Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 43.3 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm |
Sample stage | Specimen holder model: OTHER / Cooling holder cryogen: NITROGEN |