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- PDB-9njl: MARV GP in complex with MARV16 Fab -

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Basic information

Entry
Database: PDB / ID: 9njl
TitleMARV GP in complex with MARV16 Fab
Components
  • (Envelope glycoprotein ...) x 2
  • MARV16 Heavy Chain
  • MARV16 Light Chain
KeywordsVIRAL PROTEIN / Glycoprotein / Antibody / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID
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 speciesMus musculus (house mouse)
Orthomarburgvirus marburgense
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.6 Å
AuthorsAddetia, A. / Seattle Structural Genomics Center for Infectious Disease (SSGCID) / Veesler, D.
Funding support United States, 1items
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, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 26, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
H: MARV16 Heavy Chain
L: MARV16 Light Chain
A: Envelope glycoprotein GP1
B: Envelope glycoprotein GP2
I: MARV16 Heavy Chain
N: MARV16 Light Chain
C: Envelope glycoprotein GP1
D: Envelope glycoprotein GP2
J: MARV16 Heavy Chain
P: MARV16 Light Chain
E: Envelope glycoprotein GP1
F: Envelope glycoprotein GP2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)307,81327
Polymers300,84412
Non-polymers6,96915
Water97354
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

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Envelope glycoprotein ... , 2 types, 6 molecules ACEBDF

#3: Protein Envelope glycoprotein GP1 / GP1 / 2 / GP / Virion spike glycoprotein


Mass: 29689.832 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Orthomarburgvirus marburgense / Strain: Musoke / Gene: GP / Production host: Homo sapiens (human) / References: UniProt: P35253
#4: Protein Envelope glycoprotein GP2


Mass: 23432.998 Da / Num. of mol.: 3 / Mutation: W439A, F445G, F447N, H589I
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Orthomarburgvirus marburgense / Strain: Musoke / Gene: GP / Production host: Homo sapiens (human) / References: UniProt: P35253

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Antibody , 2 types, 6 molecules HIJLNP

#1: Antibody MARV16 Heavy Chain


Mass: 23921.689 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human)
#2: Antibody MARV16 Light Chain


Mass: 23236.838 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human)

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Sugars , 3 types, 15 molecules

#5: Polysaccharide beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 586.542 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5]/1-1-2/a4-b1_b4-c1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{}}}LINUCSPDB-CARE
#6: Polysaccharide alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 1072.964 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpa1-2DManpa1-3[DManpa1-6]DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/3,6,5/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5][a1122h-1a_1-5]/1-1-2-3-3-3/a4-b1_b4-c1_c3-d1_c6-f1_d2-e1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{[(3+1)][a-D-Manp]{[(2+1)][a-D-Manp]{}}[(6+1)][a-D-Manp]{}}}}LINUCSPDB-CARE
#7: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 9
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

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Non-polymers , 1 types, 54 molecules

#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 54 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: MARV GP in complex with MARV16 Fab / Type: COMPLEX / Entity ID: #3-#4, #1-#2 / Source: MULTIPLE SOURCES
Source (natural)Organism: Orthomarburgvirus marburgense / Strain: Musoke
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 400 nm
Image recordingElectron dose: 63 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM software
IDNameCategory
1Warpparticle selection
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C3 (3 fold cyclic)
3D reconstructionResolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 368509 / Symmetry type: POINT
RefinementHighest resolution: 2.6 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)

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