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- EMDB-28179: Structure of lineage II Lassa virus glycoprotein complex (strain ... -
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Open data
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Basic information
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Title | Structure of lineage II Lassa virus glycoprotein complex (strain NIG08-A41) | |||||||||
![]() | final refinement | |||||||||
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Function / homology | ![]() host cell Golgi membrane / receptor-mediated endocytosis of virus by host cell / host cell endoplasmic reticulum membrane / fusion of virus membrane with host endosome membrane / ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Perrett HR / Ward AB | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies. Authors: Hailee R Perrett / Philip J M Brouwer / Jonathan Hurtado / Maddy L Newby / Lin Liu / Helena Müller-Kräuter / Sarah Müller Aguirre / Judith A Burger / Joey H Bouhuijs / Grace Gibson / ...Authors: Hailee R Perrett / Philip J M Brouwer / Jonathan Hurtado / Maddy L Newby / Lin Liu / Helena Müller-Kräuter / Sarah Müller Aguirre / Judith A Burger / Joey H Bouhuijs / Grace Gibson / Terrence Messmer / John S Schieffelin / Aleksandar Antanasijevic / Geert-Jan Boons / Thomas Strecker / Max Crispin / Rogier W Sanders / Bryan Briney / Andrew B Ward / ![]() ![]() ![]() ![]() Abstract: Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. ...Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of recombinant GPCs and the antigenic differences among phylogenetically distinct LASV lineages. Despite the sequence diversity of the GPC, structures of most lineages are lacking. We present the development and characterization of prefusion-stabilized, trimeric GPCs of LASV lineages II, V, and VII, revealing structural conservation despite sequence diversity. High-resolution structures and biophysical characterization of the GPC in complex with GP1-A-specific antibodies suggest their neutralization mechanisms. Finally, we present the isolation and characterization of a trimer-preferring neutralizing antibody belonging to the GPC-B competition group with an epitope that spans adjacent protomers and includes the fusion peptide. Our work provides molecular detail information on LASV antigenic diversity and will guide efforts to design pan-LASV vaccines. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.5 KB 21.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 8.8 KB | Display | ![]() |
Images | ![]() | 196 KB | ||
Masks | ![]() | 64 MB | ![]() | |
Filedesc metadata | ![]() | 6.5 KB | ||
Others | ![]() ![]() ![]() | 31.9 MB 59.4 MB 59.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8ejeMC ![]() 8ejdC ![]() 8ejfC ![]() 8ejgC ![]() 8ejhC ![]() 8ejiC ![]() 8ejjC C: citing same article ( M: atomic model generated by this map |
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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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Annotation | final refinement | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.045 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: unsharpened map
File | emd_28179_additional_1.map | ||||||||||||
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Annotation | unsharpened map | ||||||||||||
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Density Histograms |
-Half map: half map A of final refinement
File | emd_28179_half_map_1.map | ||||||||||||
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Annotation | half map A of final refinement | ||||||||||||
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Density Histograms |
-Half map: half map B of final refinement
File | emd_28179_half_map_2.map | ||||||||||||
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Annotation | half map B of final refinement | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Lassa mammarenavirus GPC
Entire | Name: Lassa mammarenavirus GPC |
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Components |
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-Supramolecule #1: Lassa mammarenavirus GPC
Supramolecule | Name: Lassa mammarenavirus GPC / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 Details: GPC protein codon-optimized and expressed in HEK 293F cells using covalently-linked I53-50A trimerization scaffold. |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 275 KDa |
-Macromolecule #1: Glycoprotein GP1
Macromolecule | Name: Glycoprotein GP1 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 28.398682 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGQIITFFQE VPHVIEEVMN IVLIALSLLA ILKGIYNVAT CGLFGLVSFL LLCGRSCSTT YKGVYELQTL ELNMASLNMT MPLSCTKNN SHHYIMVGNE TGLELTLTNT SIINHKFCNL SDAHKRNLYD HALMSIISTF HLSIPNFNQY EAMSCDFNGG K ISVQYNLS ...String: MGQIITFFQE VPHVIEEVMN IVLIALSLLA ILKGIYNVAT CGLFGLVSFL LLCGRSCSTT YKGVYELQTL ELNMASLNMT MPLSCTKNN SHHYIMVGNE TGLELTLTNT SIINHKFCNL SDAHKRNLYD HALMSIISTF HLSIPNFNQY EAMSCDFNGG K ISVQYNLS HTYAVDAAKH CGTIANGVLQ TFMRMAWGGS YIALDSGCGS WDCIMTSYQY LIIQNTTWED HCQFSRPSPI GY LGLLSQR TRDIYIS UniProtKB: Pre-glycoprotein polyprotein GP complex |
-Macromolecule #2: Glycoprotein GP2
Macromolecule | Name: Glycoprotein GP2 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 19.179818 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: GTFTWTLSDS EGNETPGGYC LTRWMLIEAE LKCFGNTAVA KCNEKHDEEF CDMLRLFDFN KQAIRRLKAP AQMSIQLINK AVNALINDQ LIMKNHLRDI MCIPYCNYSK YWYLNHTVTG KTSLPRCWLV SNGSYLNETH FSDDIEQQAD NMITELLQKE Y IDRQG UniProtKB: Pre-glycoprotein polyprotein GP complex |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 12 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Concentration | 3.0 mg/mL |
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Buffer | pH: 7.4 / Details: TBS |
Grid | Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV Details: Wait time 10 s; blotting time varied between 3-7 s; blotting force of 0. |
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Electron microscopy
Microscope | TFS KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 50.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |