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- PDB-6mid: Cryo-EM structure of the ZIKV virion in complex with Fab fragment... -
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Basic information
Entry | Database: PDB / ID: 6mid | |||||||||
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Title | Cryo-EM structure of the ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195 | |||||||||
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![]() | VIRUS/IMMUNE SYSTEM / virus / monoclonal antibody / complex / VIRUS-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() immunoglobulin complex / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / negative regulation of innate immune response / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / 4 iron, 4 sulfur cluster binding ...immunoglobulin complex / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / negative regulation of innate immune response / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / 4 iron, 4 sulfur cluster binding / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / clathrin-dependent endocytosis of virus by host cell / mRNA (nucleoside-2'-O-)-methyltransferase activity / adaptive immune response / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / molecular adaptor activity / RNA helicase activity / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / protein dimerization activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / induction by virus of host autophagy / immune response / RNA-directed RNA polymerase / viral RNA genome replication / serine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / centrosome / lipid binding / viral envelope / host cell nucleus / virion attachment to host cell / GTP binding / structural molecule activity / virion membrane / ATP hydrolysis activity / proteolysis / extracellular space / extracellular region / ATP binding / membrane / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | |||||||||
![]() | Long, F. / Rossmann, M.G. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of a potent human monoclonal antibody against Zika virus targeting a quaternary epitope. Authors: Feng Long / Michael Doyle / Estefania Fernandez / Andrew S Miller / Thomas Klose / Madhumati Sevvana / Aubrey Bryan / Edgar Davidson / Benjamin J Doranz / Richard J Kuhn / Michael S Diamond ...Authors: Feng Long / Michael Doyle / Estefania Fernandez / Andrew S Miller / Thomas Klose / Madhumati Sevvana / Aubrey Bryan / Edgar Davidson / Benjamin J Doranz / Richard J Kuhn / Michael S Diamond / James E Crowe / Michael G Rossmann / ![]() Abstract: Zika virus (ZIKV) is a major human pathogen and member of the genus in the Flaviviridae family. In contrast to most other insect-transmitted flaviviruses, ZIKV also can be transmitted sexually and ...Zika virus (ZIKV) is a major human pathogen and member of the genus in the Flaviviridae family. In contrast to most other insect-transmitted flaviviruses, ZIKV also can be transmitted sexually and from mother to fetus in humans. During recent outbreaks, ZIKV infections have been linked to microcephaly, congenital disease, and Guillain-Barré syndrome. Neutralizing antibodies have potential as therapeutic agents. We report here a 4-Å-resolution cryo-electron microscopy structure of the ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195. The footprint of the ZIKV-195 Fab fragment expands across two adjacent envelope (E) protein protomers. ZIKV neutralization by this antibody is presumably accomplished by cross-linking the E proteins, which likely prevents formation of E protein trimers required for fusion of the viral and cellular membranes. A single dose of ZIKV-195 administered 5 days after virus inoculation showed marked protection against lethality in a stringent mouse model of infection. | |||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 332.1 KB | Display | ![]() |
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PDB format | ![]() | 276.4 KB | Display | ![]() |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 9131MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
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Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
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Components
#1: Protein | Mass: 54444.051 Da / Num. of mol.: 3 / Fragment: UNP residues 291-794 / Source method: isolated from a natural source Source: (natural) ![]() Strain: isolate ZIKV/Human/French Polynesia/10087PF/2013 / References: UniProt: A0A024B7W1 #2: Protein | Mass: 8496.883 Da / Num. of mol.: 3 / Fragment: UNP residues 216-290 / Source method: isolated from a natural source Source: (natural) ![]() Strain: isolate ZIKV/Human/French Polynesia/10087PF/2013 / References: UniProt: A0A024B7W1 #3: Antibody | | Mass: 14148.739 Da / Num. of mol.: 1 / Fragment: Fab variable domain / Source method: isolated from a natural source / Source: (natural) ![]() #4: Antibody | | Mass: 11750.902 Da / Num. of mol.: 1 / Fragment: Fab variable domain / Source method: isolated from a natural source / Source: (natural) ![]() #5: Polysaccharide | Source method: isolated from a genetically manipulated source |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Molecular weight | Units: MEGADALTONS / Experimental value: NO | ||||||||||||||||||||||||||||
Source (natural) |
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Details of virus | Empty: NO / Enveloped: YES / Isolate: STRAIN / Type: VIRION | ||||||||||||||||||||||||||||
Buffer solution | pH: 8 / Details: NTE buffer at pH 8.0 | ||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Fab fragments were mixed with purified mature virus particles to make complexes. | ||||||||||||||||||||||||||||
Specimen support | Details: unspecified | ||||||||||||||||||||||||||||
Vitrification | Instrument: GATAN CRYOPLUNGE 3 / Cryogen name: ETHANE / Humidity: 90 % / Chamber temperature: 298 K |
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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 |
Image recording | Electron dose: 30 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 1691 |
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Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 10687 Details: The map was masked by removing the internal nucleic acid region and the external background region. Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL Details: The occupancy of bound Fabs was low. Due to poor density, only the variable domain of Fab molecule was modeled and fit into one of the three Fab binding sites on each icosahedral asymmetric unit. | ||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6CO8 |