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- PDB-7sgd: Lassa virus glycoprotein construct(Josiah GPCysR4) recovered from... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7sgd | ||||||
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Title | Lassa virus glycoprotein construct(Josiah GPCysR4) recovered from GPC-I53-50 nanoparticle by localized reconstruction | ||||||
![]() | Josiah GPCysR4 I53-50A | ||||||
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Function / homology | ![]() host cell Golgi membrane / host cell endoplasmic reticulum membrane / receptor-mediated endocytosis of virus by host cell / virion attachment to host cell / fusion of virus membrane with host endosome membrane / ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Antanasijevic, A. / Brouwer, P.J.M. / Ward, A.B. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection. Authors: Philip J M Brouwer / Aleksandar Antanasijevic / Adam J Ronk / Helena Müller-Kräuter / Yasunori Watanabe / Mathieu Claireaux / Hailee R Perrett / Tom P L Bijl / Marloes Grobben / Jeffrey C ...Authors: Philip J M Brouwer / Aleksandar Antanasijevic / Adam J Ronk / Helena Müller-Kräuter / Yasunori Watanabe / Mathieu Claireaux / Hailee R Perrett / Tom P L Bijl / Marloes Grobben / Jeffrey C Umotoy / Angela I Schriek / Judith A Burger / Khadija Tejjani / Nicole M Lloyd / Thijs H Steijaert / Marlies M van Haaren / Kwinten Sliepen / Steven W de Taeye / Marit J van Gils / Max Crispin / Thomas Strecker / Alexander Bukreyev / Andrew B Ward / Rogier W Sanders / ![]() ![]() ![]() ![]() Abstract: The Lassa virus is endemic in parts of West Africa, and it causes hemorrhagic fever with high mortality. The development of a recombinant protein vaccine has been hampered by the instability of ...The Lassa virus is endemic in parts of West Africa, and it causes hemorrhagic fever with high mortality. The development of a recombinant protein vaccine has been hampered by the instability of soluble Lassa virus glycoprotein complex (GPC) trimers, which disassemble into monomeric subunits after expression. Here, we use two-component protein nanoparticles consisting of trimeric and pentameric subunits to stabilize GPC in a trimeric conformation. These GPC nanoparticles present twenty prefusion GPC trimers on the surface of an icosahedral particle. Cryo-EM studies of GPC nanoparticles demonstrated a well-ordered structure and yielded a high-resolution structure of an unliganded GPC. These nanoparticles induced potent humoral immune responses in rabbits and protective immunity against the lethal Lassa virus challenge in guinea pigs. Additionally, we isolated a neutralizing antibody that mapped to the putative receptor-binding site, revealing a previously undefined site of vulnerability. Collectively, these findings offer potential approaches to vaccine and therapeutic design for the Lassa virus. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 267.4 KB | Display | ![]() |
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PDB format | ![]() | 202 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 2.6 MB | Display | ![]() |
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Full document | ![]() | 2.6 MB | Display | |
Data in XML | ![]() | 44.9 KB | Display | |
Data in CIF | ![]() | 63.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 25107MC ![]() 7sgeC ![]() 7sgfC 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
-Protein , 1 types, 6 molecules AaBbCc
#1: Protein | Mass: 73845.570 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-Sugars , 5 types, 33 molecules 
#2: 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 #3: Polysaccharide | ![]() Source method: isolated from a genetically manipulated source #4: Polysaccharide | ![]() Source method: isolated from a genetically manipulated source #5: Polysaccharide | ![]() Source method: isolated from a genetically manipulated source #6: Sugar | ChemComp-NAG / ![]() |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: Lassa virus glycoprotein construct(Josiah GPCysR4) recovered from GPC-I53-50 nanoparticle Type: COMPLEX Details: Josiah GPCysR4 is a trimeric complex consisting of 3 copies of the head domain and 3 copies of the stem domain. Nanoparticle was assembled by combining equimolar amounts of GPC-I53-50A and I53-50B. Entity ID: #1 / Source: RECOMBINANT | |||||||||||||||
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Molecular weight | Experimental value: NO | |||||||||||||||
Source (natural) | Organism: ![]() ![]() | |||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | |||||||||||||||
Buffer solution | pH: 7 / Details: TBS | |||||||||||||||
Buffer component |
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Specimen | Conc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() Details: Lassa virus glycoprotein construct(Josiah GPCysR4) recovered from GPC-I53-50 nanoparticle by localized reconstruction. Nanoparticle was assembled by combining equimolar amounts of GPC-I53-50A and I53-50B. | |||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R2/1 | |||||||||||||||
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 283 K / Details: Blot time 4s, Wait time 10s, Blot force 0 |
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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![]() ![]() |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 10.5 sec. / Electron dose: 50.4 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 2 |
Image scans | Movie frames/image: 42 |
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Processing
EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1728229 Details: This is the number of GPCysR4 trimer subparticles extracted from the GPC-I53-50 nanoparticle by localized reconstruction: 86,411 nanoparticles X 20 = 1728229. | ||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 3.97 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 124891 / Algorithm: BACK PROJECTION Details: C3 symmetry used for refinement. Solvent mask applied. Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 5VK2 |