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- PDB-7ul7: Lineage I (Pinneo) Lassa virus glycoprotein bound to 18.5C-M30 Fab -
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Open data
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Basic information
Entry | Database: PDB / ID: 7ul7 | ||||||||||||
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Title | Lineage I (Pinneo) Lassa virus glycoprotein bound to 18.5C-M30 Fab | ||||||||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / glycoprotein / antibody / lassa virus / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||||||||
Function / homology | ![]() host cell Golgi membrane / membrane => GO:0016020 / receptor-mediated endocytosis of virus by host cell / 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 / metal ion binding Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.59 Å | ||||||||||||
![]() | Buck, T.K. / Enriquez, A.S. / Hastie, K.M. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Neutralizing Antibodies against Lassa Virus Lineage I. Authors: Tierra K Buck / Adrian S Enriquez / Sharon L Schendel / Michelle A Zandonatti / Stephanie S Harkins / Haoyang Li / Alex Moon-Walker / James E Robinson / Luis M Branco / Robert F Garry / ...Authors: Tierra K Buck / Adrian S Enriquez / Sharon L Schendel / Michelle A Zandonatti / Stephanie S Harkins / Haoyang Li / Alex Moon-Walker / James E Robinson / Luis M Branco / Robert F Garry / Erica Ollmann Saphire / Kathryn M Hastie / ![]() Abstract: Lassa virus (LASV) is the causative agent of the deadly Lassa fever (LF). Seven distinct LASV lineages circulate through western Africa, among which lineage I (LI), the first to be identified, is ...Lassa virus (LASV) is the causative agent of the deadly Lassa fever (LF). Seven distinct LASV lineages circulate through western Africa, among which lineage I (LI), the first to be identified, is particularly resistant to antibody neutralization. Lineage I LASV evades neutralization by half of known antibodies in the GPC-A antibody competition group and all but one of the antibodies in the GPC-B competition group. Here, we solve two cryo-electron microscopy (cryo-EM) structures of LI GP in complex with a GPC-A and a GPC-B antibody. We used complementary structural and biochemical techniques to identify single-amino-acid substitutions in LI that are responsible for immune evasion by each antibody group. Further, we show that LI infection is more dependent on the endosomal receptor lysosome-associated membrane protein 1 (LAMP1) for viral entry relative to LIV. In the absence of LAMP1, LI requires a more acidic fusion pH to initiate membrane fusion with the host cell relative to LIV. No vaccine or therapeutics are approved to prevent LASV infection or treat LF. All vaccine platforms currently under development present only the LIV GP sequence. However, our data suggest that the high genetic diversity of LASV may be problematic for designing both a broadly reactive immunogen and therapeutic. Here, we examine antibodies that are highly potent against LIV yet are ineffective against LI. By pinpointing LI mutations responsible for this decrease in antibody efficacy, we suggest that future vaccine platforms may need to incorporate specific LI-like mutations in order to generate a broadly neutralizing antibody response against all LASV lineages. | ||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 469.2 KB | Display | ![]() |
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PDB format | ![]() | 377.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.6 MB | Display | ![]() |
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Full document | ![]() | 1.6 MB | Display | |
Data in XML | ![]() | 81.4 KB | Display | |
Data in CIF | ![]() | 118.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 26594MC ![]() 7udsC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Glycoprotein ... , 2 types, 6 molecules CABcba
#1: Protein | Mass: 28987.398 Da / Num. of mol.: 3 / Mutation: Residues 255-258 mutated from RRLL to RRRR Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #4: Protein | Mass: 23348.145 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Antibody , 2 types, 6 molecules DLFEHG
#2: Antibody | Mass: 25880.822 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #3: Antibody | Mass: 26737.285 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Sugars , 2 types, 26 molecules ![](data/chem/img/NAG.gif)
#5: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #6: Sugar | ChemComp-NAG / |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Lineage I (Pinneo) Lassa virus glycoprotein bound to 18.5C-M30 Fab Type: COMPLEX / Entity ID: #1-#4 / Source: MULTIPLE SOURCES | |||||||||||||||
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Molecular weight | Value: 0.35 MDa / Experimental value: YES | |||||||||||||||
Buffer solution | pH: 7.5 | |||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Symmetry | Point symmetry: C3 (3 fold cyclic) |
3D reconstruction | Resolution: 3.59 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 380210 / Symmetry type: POINT |