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- EMDB-28184: Lassa virus glycoprotein complex (Josiah) bound to S370.7 Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-28184
TitleLassa virus glycoprotein complex (Josiah) bound to S370.7 Fab
Map data
Sample
  • Complex: Lassa mammarenavirus GPC
    • Protein or peptide: Glycoprotein GP1
    • Protein or peptide: S370.7 heavy chain Fab
    • Protein or peptide: S370.7 light chain Fab
    • Protein or peptide: Glycoprotein GP2
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: alpha-D-mannopyranose
Keywordsglycoprotein complex / Lassa mammarenavirus / LASV / GPC / immune system / viral fusion protein / Lassa virus / lineage IV / Josiah / S370.7 / VIRAL PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


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 / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / membrane / metal ion binding
Similarity search - Function
Arenavirus glycoprotein, zinc binding domain / Arenavirus glycoprotein / Arenavirus glycoprotein
Similarity search - Domain/homology
Pre-glycoprotein polyprotein GP complex
Similarity search - Component
Biological speciesLassa mammarenavirus / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.22 Å
AuthorsPerrett HR / Ward AB
Funding support United States, 2 items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationINV-004923 United States
Bill & Melinda Gates FoundationOPP1170236 United States
CitationJournal: Cell Rep / Year: 2023
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
DepositionSep 16, 2022-
Header (metadata) releaseJun 7, 2023-
Map releaseJun 7, 2023-
UpdateOct 16, 2024-
Current statusOct 16, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_28184.png

Downloads & links

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Map

FileDownload / File: emd_28184.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.15 Å/pix.
x 300 pix.
= 345. Å		1.15 Å/pix.
x 300 pix.
= 345. Å		1.15 Å/pix.
x 300 pix.
= 345. Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.15 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.25
Minimum - Maximum-0.6643293 - 1.6266317
Average (Standard dev.)0.0012951348 (±0.02888356)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 345.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_28184_msk_1.map
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Additional map: #1

Fileemd_28184_additional_1.map
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Half map: #2

Fileemd_28184_half_map_1.map
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Half map: #1

Fileemd_28184_half_map_2.map
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Sample components

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Entire : Lassa mammarenavirus GPC

EntireName: Lassa mammarenavirus GPC
Components
  • Complex: Lassa mammarenavirus GPC
    • Protein or peptide: Glycoprotein GP1
    • Protein or peptide: S370.7 heavy chain Fab
    • Protein or peptide: S370.7 light chain Fab
    • Protein or peptide: Glycoprotein GP2
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: alpha-D-mannopyranose

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Supramolecule #1: Lassa mammarenavirus GPC

SupramoleculeName: Lassa mammarenavirus GPC / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Details: GPC protein codon-optimized and expressed in HEK 293F cells using covalently-linked I53-50A trimerization scaffold bound to S370.7 Fab
Source (natural)Organism: Lassa mammarenavirus / Strain: Josiah
Molecular weightTheoretical: 425 KDa

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Macromolecule #1: Glycoprotein GP1

MacromoleculeName: Glycoprotein GP1 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Lassa mammarenavirus
Molecular weightTheoretical: 22.199053 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: TSLYKGVYEL QTLELNMETL NMTMPLSCTK NNSHHYIMVG NETGLELTLT NTSIINHKFC NLSDAHKKNL YDHALMSIIS TFHLSIPNF NQYEAMSCDF NGGKISVQYN LSHSYAGDAA NHCGTVANGV LQTFMRMAWG GSYIALDSGC GNWDCIMTSY Q YLIIQNTT ...String:
TSLYKGVYEL QTLELNMETL NMTMPLSCTK NNSHHYIMVG NETGLELTLT NTSIINHKFC NLSDAHKKNL YDHALMSIIS TFHLSIPNF NQYEAMSCDF NGGKISVQYN LSHSYAGDAA NHCGTVANGV LQTFMRMAWG GSYIALDSGC GNWDCIMTSY Q YLIIQNTT WEDHCQFSRP SPIGYLGLLS QRTRDIYIS

UniProtKB: Pre-glycoprotein polyprotein GP complex

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Macromolecule #2: S370.7 heavy chain Fab

MacromoleculeName: S370.7 heavy chain Fab / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 14.109716 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QVHLQQWGTG LLKPSETLSL TCAVYGGSIS SYYWSWIRQP PGKGLEWIGE ISHSGSTNYN PSLKSRVTIS VDTSKNQLSL KLRSVTAAD TAVYYCARGR DCRSVSCYVS SPENWFDPWG QGTPITVSS

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Macromolecule #3: S370.7 light chain Fab

MacromoleculeName: S370.7 light chain Fab / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 11.517611 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
YELTQPPSVS VSPGQTARIT CSGDALPKQY AYWYQQKPGQ APVMVIYKDS ERPSGIPERF SGSNSGTTVT LTISGVQAED EADYYCQSA DSDGTYRVFG GGTKVTVL

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Macromolecule #4: Glycoprotein GP2

MacromoleculeName: Glycoprotein GP2 / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Lassa mammarenavirus
Molecular weightTheoretical: 19.146824 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
GTFTWTLSDS EGKDTPGGYC LTRWMLIEAE LKCFGNTAVA KCNEKHDEEF CDMLRLFDFN KQAIQRLKAP AQMSIQLINK AVNALINDQ LIMKNHLRDI MCIPYCNYSK YWYLNHTTTG RTSLPKCWLV SNGSYLNETH FSDDIEQQAD NMITEMLQKE Y MERQ

UniProtKB: Pre-glycoprotein polyprotein GP complex

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Macromolecule #11: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 11 / Number of copies: 6 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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Macromolecule #12: alpha-D-mannopyranose

MacromoleculeName: alpha-D-mannopyranose / type: ligand / ID: 12 / Number of copies: 1 / Formula: MAN
Molecular weightTheoretical: 180.156 Da
Chemical component information

ChemComp-MAN:
alpha-D-mannopyranose

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration3.0 mg/mL
BufferpH: 7.4 / Details: TBS
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen 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

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 50.11 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.7000000000000001 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

7sgd

Final reconstructionApplied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.22 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 3.2) / Number images used: 96449
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.2)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.2)
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelPDB ID:

7sgd


Chain - Source name: PDB / Chain - Initial model type: experimental model
Output model

PDB-8ejj:
Lassa virus glycoprotein complex (Josiah) bound to S370.7 Fab

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