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- EMDB-49486: MARV GP in complex with MARV16 Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-49486
TitleMARV GP in complex with MARV16 Fab
Map data
Sample
  • Complex: MARV GP in complex with MARV16 Fab
    • Protein or peptide: Envelope glycoprotein GP1
    • Protein or peptide: Envelope glycoprotein GP2
    • Protein or peptide: MARV16 Heavy Chain
    • Protein or peptide: MARV16 Light Chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: water
KeywordsGlycoprotein / Antibody / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / VIRAL PROTEIN
Function / homology
Function and homology information


fusion of virus membrane with host endosome membrane / viral envelope / symbiont entry into host cell / virion attachment to host cell / host cell plasma membrane / virion membrane / membrane
Similarity search - Function
TLV/ENV coat polyprotein / : / Filoviruses glycoprotein, extracellular domain / Filoviruses glycoprotein / Filovirus glycoprotein / Envelope glycoprotein GP2-like, HR1-HR2
Similarity search - Domain/homology
Envelope glycoprotein
Similarity search - Component
Biological speciesOrthomarburgvirus marburgense / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.6 Å
AuthorsAddetia A / Seattle Structural Genomics Center for Infectious Disease (SSGCID) / Veesler D
Funding support United States, 1 items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI) United States
CitationJournal: Nature / Year: 2025
Title: Potent neutralization of Marburg virus by a vaccine-elicited antibody.
Authors: Amin Addetia / Lisa Perruzza / Kaitlin Sprouse / Young-Jun Park / Matthew McCallum / Cameron Stewart / Bianca Partini / Jack T Brown / Alessia Donati / Katja Culap / Alessio Balmelli / ...Authors: Amin Addetia / Lisa Perruzza / Kaitlin Sprouse / Young-Jun Park / Matthew McCallum / Cameron Stewart / Bianca Partini / Jack T Brown / Alessia Donati / Katja Culap / Alessio Balmelli / Bhavna Chawla / Swagata Kar / Michal Gazi / Kendra Alfson / Yenny Goez-Gazi / Ricardo Carrion / Davide Corti / Fabio Benigni / David Veesler /
Abstract: Marburg virus (MARV) is a filovirus that causes severe and often lethal haemorrhagic fever. Despite the increasing frequency of MARV outbreaks, no vaccines or therapeutics are licensed for use in ...Marburg virus (MARV) is a filovirus that causes severe and often lethal haemorrhagic fever. Despite the increasing frequency of MARV outbreaks, no vaccines or therapeutics are licensed for use in humans. Here we designed mutations that improve the expression, thermostability and immunogenicity of the prefusion MARV glycoprotein (GP) ectodomain trimer, which is the sole target of neutralizing antibodies and vaccines in development. We discovered a fully human, pan-marburgvirus monoclonal antibody, MARV16, that broadly neutralizes all MARV isolates, Ravn virus and Dehong virus with 40-100-fold increased potency relative to previously described antibodies. Moreover, MARV16 provided therapeutic protection in guinea pigs challenged with MARV. We determined a cryogenic electron microscopy structure of MARV16-bound MARV GP. The structure shows that MARV16 recognizes a prefusion-specific epitope spanning GP1 and GP2, which blocks receptor binding and prevents conformational changes required for viral entry. We further determined the architecture of the MARV GP glycan cap, which shields the receptor-binding site, and identified architectural similarities with distantly related filovirus GPs. MARV16 and previously identified antibodies directed against the receptor-binding site simultaneously bound MARV GP. These antibody cocktails required multiple mutations to escape neutralization by both antibodies, a result that paves the way for the development of MARV therapeutics resistant to viral evolution. MARV GP stabilization along with the discovery of MARV16 advance prevention and treatment options for MARV disease.
History
DepositionFeb 27, 2025-
Header (metadata) releaseNov 26, 2025-
Map releaseNov 26, 2025-
UpdateNov 26, 2025-
Current statusNov 26, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_49486.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 512 pix.
= 424.448 Å
0.83 Å/pix.
x 512 pix.
= 424.448 Å
0.83 Å/pix.
x 512 pix.
= 424.448 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.829 Å
Density
Contour LevelBy AUTHOR: 0.25
Minimum - Maximum-3.5493736 - 4.7490444
Average (Standard dev.)0.0006172835 (±0.03878392)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 424.448 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_49486_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_49486_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : MARV GP in complex with MARV16 Fab

EntireName: MARV GP in complex with MARV16 Fab
Components
  • Complex: MARV GP in complex with MARV16 Fab
    • Protein or peptide: Envelope glycoprotein GP1
    • Protein or peptide: Envelope glycoprotein GP2
    • Protein or peptide: MARV16 Heavy Chain
    • Protein or peptide: MARV16 Light Chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: water

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Supramolecule #1: MARV GP in complex with MARV16 Fab

SupramoleculeName: MARV GP in complex with MARV16 Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #3-#4, #1-#2
Source (natural)Organism: Orthomarburgvirus marburgense / Strain: Musoke

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Macromolecule #1: MARV16 Heavy Chain

MacromoleculeName: MARV16 Heavy Chain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 23.921689 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: EVQLVESGGG LVKPGGSLRL SCAASGFTFS SYTMNWVRQA PGKGLEWVSS ISSSESYIYY VDSVQGRFTI SRDNAKNSLY LQLNSLRAE DTAVYYCVRR DNWNYDTLDI WGQGTMVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS ...String:
EVQLVESGGG LVKPGGSLRL SCAASGFTFS SYTMNWVRQA PGKGLEWVSS ISSSESYIYY VDSVQGRFTI SRDNAKNSLY LQLNSLRAE DTAVYYCVRR DNWNYDTLDI WGQGTMVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKRV EPKSC

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Macromolecule #2: MARV16 Light Chain

MacromoleculeName: MARV16 Light Chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 23.236838 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DIVMTQSPSS LSASVGDRVI ITCRASQSIS TYLNWYQQKP GKAPKLLIYA ASSLQSGVPS RFSGSESGTD FTLTISGLQP EDFATYYCL QSYDAPLTFG GGTKVDIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String:
DIVMTQSPSS LSASVGDRVI ITCRASQSIS TYLNWYQQKP GKAPKLLIYA ASSLQSGVPS RFSGSESGTD FTLTISGLQP EDFATYYCL QSYDAPLTFG GGTKVDIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC

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Macromolecule #3: Envelope glycoprotein GP1

MacromoleculeName: Envelope glycoprotein GP1 / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Orthomarburgvirus marburgense / Strain: Musoke
Molecular weightTheoretical: 29.689832 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKTTCFLISL ILIQGTKNLP ILEIASNNQP QNVDSVCSGT LQKTEDVHLM GFTLSGQKVA DSPLEASKRW AFRTGVPPKN VEYTEGEEA KTCYNISVTD PSGKSLLLDP PTNIRDYPKC KTIHHIQGQN PHAQGIALHL WGAFFLYDRI ASTTMYRGKV F TEGNIAAM ...String:
MKTTCFLISL ILIQGTKNLP ILEIASNNQP QNVDSVCSGT LQKTEDVHLM GFTLSGQKVA DSPLEASKRW AFRTGVPPKN VEYTEGEEA KTCYNISVTD PSGKSLLLDP PTNIRDYPKC KTIHHIQGQN PHAQGIALHL WGAFFLYDRI ASTTMYRGKV F TEGNIAAM IVNKTVHKMI FSRQGQGYRH MNLTSTNKYW TSSNGTQTND TGCFGALQEY NSTKNQTCAP SKIPPPLPTA RP EIKLTST PTDATKLNTQ HLVYFRRKR

UniProtKB: Envelope glycoprotein

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Macromolecule #4: Envelope glycoprotein GP2

MacromoleculeName: Envelope glycoprotein GP2 / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Orthomarburgvirus marburgense / Strain: Musoke
Molecular weightTheoretical: 23.432998 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SILAREGDMG PNLDGLINAP IDFDPVPNTK TIFDESSSSG ASAEEDQHAS PNISLTLSYF PNINENTAYS GENENDCDAE LRIWSVQED DLAAGLSWIP FFGPGIEGLY TAVLIKNQNN LVCRLRRLAN QTAKSLELLL RVTTEERTFS LINRIAIDFL L TRWGGTCK ...String:
SILAREGDMG PNLDGLINAP IDFDPVPNTK TIFDESSSSG ASAEEDQHAS PNISLTLSYF PNINENTAYS GENENDCDAE LRIWSVQED DLAAGLSWIP FFGPGIEGLY TAVLIKNQNN LVCRLRRLAN QTAKSLELLL RVTTEERTFS LINRIAIDFL L TRWGGTCK VLGPDCCIGI EDLSKNISEQ IDQIKKDEQK EGTGSHHHHH HHH

UniProtKB: Envelope glycoprotein

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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: 9 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

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

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Macromolecule #8: water

MacromoleculeName: water / type: ligand / ID: 8 / Number of copies: 54 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

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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: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 63.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.4 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:
Final reconstructionApplied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 368509
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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