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Yorodumi- PDB-6w1c: Human mAbs broadly protect against infection of arthritiogenic al... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6w1c | ||||||
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Title | Human mAbs broadly protect against infection of arthritiogenic alphaviruses by recognizing conserved elements of the MXR8 receptor binding domain | ||||||
Components |
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Keywords | VIRUS/IMMUNE SYSTEM / virus / monoclonal antibody / complex / VIRUS-IMMUNE SYSTEM complex | ||||||
Function / homology | Function and homology information togavirin / T=4 icosahedral viral capsid / symbiont-mediated suppression of host toll-like receptor signaling pathway / host cell cytoplasm / symbiont entry into host cell / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / host cell nucleus / virion attachment to host cell / host cell plasma membrane ...togavirin / T=4 icosahedral viral capsid / symbiont-mediated suppression of host toll-like receptor signaling pathway / host cell cytoplasm / symbiont entry into host cell / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / host cell nucleus / virion attachment to host cell / host cell plasma membrane / structural molecule activity / virion membrane / proteolysis / RNA binding / membrane Similarity search - Function | ||||||
Biological species | Mayaro virus Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 5.3 Å | ||||||
Authors | Miller, A.S. / Kuhn, R.J. | ||||||
Funding support | United States, 1items
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Citation | Journal: Cell Host Microbe / Year: 2020 Title: Human mAbs Broadly Protect against Arthritogenic Alphaviruses by Recognizing Conserved Elements of the Mxra8 Receptor-Binding Site. Authors: Laura A Powell / Andrew Miller / Julie M Fox / Nurgun Kose / Thomas Klose / Arthur S Kim / Robin Bombardi / Rashika N Tennekoon / A Dharshan de Silva / Robert H Carnahan / Michael S Diamond ...Authors: Laura A Powell / Andrew Miller / Julie M Fox / Nurgun Kose / Thomas Klose / Arthur S Kim / Robin Bombardi / Rashika N Tennekoon / A Dharshan de Silva / Robert H Carnahan / Michael S Diamond / Michael G Rossmann / Richard J Kuhn / James E Crowe / Abstract: Mosquito inoculation of humans with arthritogenic alphaviruses results in a febrile syndrome characterized by debilitating musculoskeletal pain and arthritis. Despite an expanding global disease ...Mosquito inoculation of humans with arthritogenic alphaviruses results in a febrile syndrome characterized by debilitating musculoskeletal pain and arthritis. Despite an expanding global disease burden, no approved therapies or licensed vaccines exist. Here, we describe human monoclonal antibodies (mAbs) that bind to and neutralize multiple distantly related alphaviruses. These mAbs compete for an antigenic site and prevent attachment to the recently discovered Mxra8 alphavirus receptor. Three cryoelectron microscopy structures of Fab in complex with Ross River (RRV), Mayaro, or chikungunya viruses reveal a conserved footprint of the broadly neutralizing mAb RRV-12 in a region of the E2 glycoprotein B domain. This mAb neutralizes virus in vitro by preventing virus entry and spread and is protective in vivo in mouse models. Thus, the RRV-12 mAb and its defined epitope have potential as a therapeutic agent or target of vaccine design against multiple emerging arthritogenic alphavirus infections. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6w1c.cif.gz | 565 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6w1c.ent.gz | 376.5 KB | Display | PDB format |
PDBx/mmJSON format | 6w1c.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6w1c_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 6w1c_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 6w1c_validation.xml.gz | 106.2 KB | Display | |
Data in CIF | 6w1c_validation.cif.gz | 173.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/w1/6w1c ftp://data.pdbj.org/pub/pdb/validation_reports/w1/6w1c | HTTPS FTP |
-Related structure data
Related structure data | 21509MC 6vyvC 6w09C 6w2uC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
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Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
-Components
#1: Protein | Mass: 41612.867 Da / Num. of mol.: 4 / Fragment: UNP residues 807-1186 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mayaro virus (strain Brazil) / Strain: Brazil / Production host: Homo sapiens (human) / References: UniProt: Q8QZ72 #2: Protein | Mass: 38041.957 Da / Num. of mol.: 4 / Fragment: UNP residues 325-664 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mayaro virus (strain Brazil) / Strain: Brazil / Production host: Homo sapiens (human) / References: UniProt: Q8QZ72 #3: Antibody | Mass: 23743.719 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Hybridoma / Production host: Homo sapiens (human) #4: Antibody | Mass: 22888.404 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Hybridoma / Production host: Homo sapiens (human) |
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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 |
-Sample preparation
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Source (natural) |
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Source (recombinant) |
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Details of virus | Empty: NO / Enveloped: YES / Isolate: STRAIN / Type: VIRION | ||||||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid type: C-flat | ||||||||||||||||||||||||
Vitrification | Instrument: GATAN CRYOPLUNGE 3 / Cryogen name: ETHANE / Humidity: 85 % |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 18000 X / Cs: 2.7 mm / C2 aperture diameter: 100 µm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 30 e/Å2 / Film or detector model: GATAN K2 BASE (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 5.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 18410 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT |