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- EMDB-27538: Lymphocytic choriomeningitis virus glycoprotein in complex with n... -

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Basic information

Entry
Database: EMDB / ID: EMD-27538
TitleLymphocytic choriomeningitis virus glycoprotein in complex with neutralizing antibody M28
Map dataLymphocytic choriomeningitis virus glycoprotein in complex with a neutralizing antibody
Sample
  • Complex: Lymphocytic choriomeningitis virus glycoprotein in complex with neutralizing antibody M28
    • Complex: Glycoprotein
      • Protein or peptide: Glycoprotein G1
      • Protein or peptide: Glycoprotein G2,Cobalamin adenosyltransferase-like domain-containing protein trimerization tag
    • Complex: 18.5C-M28 Fab Light Chain, 18.5C-M28 Fab Heavy Chain
      • Protein or peptide: 18.5C-M28 Fab Light Chain
      • Protein or peptide: 18.5C-M28 Fab Heavy Chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Function / homology
Function and homology information


corrinoid adenosyltransferase activity / 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 / ATP binding ...corrinoid adenosyltransferase activity / 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 / ATP binding / membrane / metal ion binding
Similarity search - Function
Cobalamin adenosyltransferase-like / Corrinoid adenosyltransferase, PduO-type / Cobalamin adenosyltransferase / Cobalamin adenosyltransferase-like superfamily / Arenavirus glycoprotein, zinc binding domain / Arenavirus glycoprotein / Arenavirus glycoprotein
Similarity search - Domain/homology
Pre-glycoprotein polyprotein GP complex / Cobalamin adenosyltransferase-like domain-containing protein
Similarity search - Component
Biological speciesLymphocytic choriomeningitis mammarenavirus / Homo sapiens (human) / Lymphocytic choriomeningitis virus
Methodsingle particle reconstruction / cryo EM / Resolution: 3.19 Å
AuthorsMoon-Walker A / Hastie KM / Zyla DS / Saphire EO
Funding support United States, Switzerland, 9 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)U19 AI 142790 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01 A1132244 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01AI14125 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R21AI137809 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)F31-AI154700 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)T32-AI125179 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)P01 AI145815 United States
Swiss National Science FoundationP2EZP3_195680 Switzerland
Swiss National Science FoundationP500PB_210992 Switzerland
CitationJournal: Cell Chem Biol / Year: 2023
Title: Structural basis for antibody-mediated neutralization of lymphocytic choriomeningitis virus.
Authors: Alex Moon-Walker / Zeli Zhang / Dawid S Zyla / Tierra K Buck / Haoyang Li / Ruben Diaz Avalos / Sharon L Schendel / Kathryn M Hastie / Shane Crotty / Erica Ollmann Saphire /
Abstract: The mammarenavirus lymphocytic choriomeningitis virus (LCMV) is a globally distributed zoonotic pathogen that can be lethal in immunocompromised patients and can cause severe birth defects if ...The mammarenavirus lymphocytic choriomeningitis virus (LCMV) is a globally distributed zoonotic pathogen that can be lethal in immunocompromised patients and can cause severe birth defects if acquired during pregnancy. The structure of the trimeric surface glycoprotein, essential for entry, vaccine design, and antibody neutralization, remains unknown. Here, we present the cryoelectron microscopy (cryo-EM) structure of the LCMV surface glycoprotein (GP) in its trimeric pre-fusion assembly both alone and in complex with a rationally engineered monoclonal neutralizing antibody termed 18.5C-M28 (M28). Additionally, we show that passive administration of M28, either as a prophylactic or therapeutic, protects mice from LCMV clone 13 (LCMV) challenge. Our study illuminates not only the overall structural organization of LCMV GP and the mechanism for its inhibition by M28 but also presents a promising therapeutic candidate to prevent severe or fatal disease in individuals who are at risk of infection by a virus that poses a threat worldwide.
History
DepositionJul 8, 2022-
Header (metadata) releaseApr 12, 2023-
Map releaseApr 12, 2023-
UpdateMay 3, 2023-
Current statusMay 3, 2023Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_27538.png

Downloads & links

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Map

FileDownload / File: emd_27538.map.gz / Format: CCP4 / Size: 137.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationLymphocytic choriomeningitis virus glycoprotein in complex with a neutralizing antibody
Voxel sizeX=Y=Z: 1.2 Å
Density
Contour LevelBy AUTHOR: 0.01
Minimum - Maximum-0.019314488 - 0.052622233
Average (Standard dev.)2.396164e-06 (±0.0011000187)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions330330330
Spacing330330330
CellA=B=C: 396.00003 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_27538_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Additional map: Lymphocytic choriomeningitis virus glycoprotein in complex with a...

Fileemd_27538_additional_1.map
AnnotationLymphocytic choriomeningitis virus glycoprotein in complex with a neutralizing antibody
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Lymphocytic choriomeningitis virus glycoprotein in complex with a...

Fileemd_27538_half_map_1.map
AnnotationLymphocytic choriomeningitis virus glycoprotein in complex with a neutralizing antibody
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Lymphocytic choriomeningitis virus glycoprotein in complex with a...

Fileemd_27538_half_map_2.map
AnnotationLymphocytic choriomeningitis virus glycoprotein in complex with a neutralizing antibody
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Lymphocytic choriomeningitis virus glycoprotein in complex with n...

EntireName: Lymphocytic choriomeningitis virus glycoprotein in complex with neutralizing antibody M28
Components
  • Complex: Lymphocytic choriomeningitis virus glycoprotein in complex with neutralizing antibody M28
    • Complex: Glycoprotein
      • Protein or peptide: Glycoprotein G1
      • Protein or peptide: Glycoprotein G2,Cobalamin adenosyltransferase-like domain-containing protein trimerization tag
    • Complex: 18.5C-M28 Fab Light Chain, 18.5C-M28 Fab Heavy Chain
      • Protein or peptide: 18.5C-M28 Fab Light Chain
      • Protein or peptide: 18.5C-M28 Fab Heavy Chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Lymphocytic choriomeningitis virus glycoprotein in complex with n...

SupramoleculeName: Lymphocytic choriomeningitis virus glycoprotein in complex with neutralizing antibody M28
type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#4

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Supramolecule #2: Glycoprotein

SupramoleculeName: Glycoprotein / type: complex / ID: 2 / Chimera: Yes / Parent: 1 / Macromolecule list: #1, #4
Source (natural)Organism: Lymphocytic choriomeningitis mammarenavirus

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Supramolecule #3: 18.5C-M28 Fab Light Chain, 18.5C-M28 Fab Heavy Chain

SupramoleculeName: 18.5C-M28 Fab Light Chain, 18.5C-M28 Fab Heavy Chain / type: complex / ID: 3 / Chimera: Yes / Parent: 1 / Macromolecule list: #2-#3
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Glycoprotein G1

MacromoleculeName: Glycoprotein G1 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Lymphocytic choriomeningitis virus / Strain: Clone 13
Molecular weightTheoretical: 25.52116 KDa
Recombinant expressionOrganism: Drosophila melanogaster (fruit fly)
SequenceString: MKLCILLAVV AFVGLSLGMY GLKGPDIYKG VYQFKSVEFD MSHLNLTMPN ACSANNSHHY ISMGTSGLEL TFTNDSIISH NFCNLTSAF NKKTFDHTLM SIVSSLHLSI RGNSNYKAVS CDFNNGITIQ YNLTFSDAQS AQSQCRTFRG RVLDMFRTAF G GKYMRSCW ...String:
MKLCILLAVV AFVGLSLGMY GLKGPDIYKG VYQFKSVEFD MSHLNLTMPN ACSANNSHHY ISMGTSGLEL TFTNDSIISH NFCNLTSAF NKKTFDHTLM SIVSSLHLSI RGNSNYKAVS CDFNNGITIQ YNLTFSDAQS AQSQCRTFRG RVLDMFRTAF G GKYMRSCW GWTGSDGKTT WCSQTSYQYL IIQNRTWENH CTYAGPFGMS RILLSQEKTK FLTRRRR

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Macromolecule #2: 18.5C-M28 Fab Light Chain

MacromoleculeName: 18.5C-M28 Fab Light Chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.306834 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: DIVLTQSPGT LSLSPGERAT LSCRASQSVI SYYVAWYQHK GGQAPRLLIY GASSRATGVP DRFSGSGSGT DFTLTISSLE PEDFALYYC QYYGSSPLWA FGQGTKVEIK RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ ...String:
DIVLTQSPGT LSLSPGERAT LSCRASQSVI SYYVAWYQHK GGQAPRLLIY GASSRATGVP DRFSGSGSGT DFTLTISSLE PEDFALYYC QYYGSSPLWA FGQGTKVEIK RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ DSKDSTYSLS STLTLSKADY EKHKVYACEV THQGLSSPVT KSFNRG

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Macromolecule #3: 18.5C-M28 Fab Heavy Chain

MacromoleculeName: 18.5C-M28 Fab Heavy Chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.610715 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: DEVQLVQSGG GLVRPGGSLR LSCAAAGFTF KRYSMNWVRQ APGRGLEWVS SITSRGGSKT YYADVVKGRF TVSRDNAKQS LYLQMNSLR AEDTAIYFCA RSLHSTSQPS YMDVWGRKIT VIVSSASTKG PSVFPLAPSG GTAALGCLVK DYFPEPVTVS W NSGALTSG ...String:
DEVQLVQSGG GLVRPGGSLR LSCAAAGFTF KRYSMNWVRQ APGRGLEWVS SITSRGGSKT YYADVVKGRF TVSRDNAKQS LYLQMNSLR AEDTAIYFCA RSLHSTSQPS YMDVWGRKIT VIVSSASTKG PSVFPLAPSG GTAALGCLVK DYFPEPVTVS W NSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKRVE PK

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Macromolecule #4: Glycoprotein G2,Cobalamin adenosyltransferase-like domain-contain...

MacromoleculeName: Glycoprotein G2,Cobalamin adenosyltransferase-like domain-containing protein trimerization tag
type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Lymphocytic choriomeningitis virus / Strain: Clone 13
Molecular weightTheoretical: 42.166777 KDa
Recombinant expressionOrganism: Drosophila melanogaster (fruit fly)
SequenceString: GTFTWTLSDS SGVENPGGYC LTKWMILAAE LKCFGNTAVA KCNVNHDEEF CDMLRLIDYN KAALSKFKPD VESALHLFKT TVNSLISDQ LLMRNHLRDL MCVPYCNYSK FWYLEHAKTG ETSVPKCWLV TNGAYLNETH FSDQIEQEAD NMITEMLRKD Y IKRQGLEG ...String:
GTFTWTLSDS SGVENPGGYC LTKWMILAAE LKCFGNTAVA KCNVNHDEEF CDMLRLIDYN KAALSKFKPD VESALHLFKT TVNSLISDQ LLMRNHLRDL MCVPYCNYSK FWYLEHAKTG ETSVPKCWLV TNGAYLNETH FSDQIEQEAD NMITEMLRKD Y IKRQGLEG GSPVVEVQGT IDELNSFIGY ALVLSRWDDI RNDLFRIQND LFVLGEDVST GGKGRTVTRE MIDYLEARVK EM KAEIGKI ELFVVPGGSV ESASLHMARA VSRRLERRIV AASKLTEINK NVLIYANRLS SILFMHALIS NKRLNIPEKI WAL EVDDDD KAGWSHPQFE KGGGSGGGSG GGSWSHPQFE KGSGGLNDIF EAQKIEWHE

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Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 7 / 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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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.19 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 34783
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE

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