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- EMDB-21509: Human mAbs broadly protect against infection of arthritiogenic al... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-21509 | |||||||||
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Title | Human mAbs broadly protect against infection of arthritiogenic alphaviruses by recognizing conserved elements of the MXR8 receptor binding domain | |||||||||
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![]() | virus / monoclonal antibody / complex / VIRUS-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() 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 | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 5.3 Å | |||||||||
![]() | Miller AS / Kuhn RJ | |||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 279.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 20.2 KB 20.2 KB | Display Display | ![]() |
Images | ![]() | 199.6 KB | ||
Filedesc metadata | ![]() | 6.3 KB | ||
Others | ![]() ![]() | 279.7 MB 279.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6w1cMC ![]() 6vyvC ![]() 6w09C ![]() 6w2uC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | unsharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.62 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: half map 1, unsharpened
File | emd_21509_half_map_1.map | ||||||||||||
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Annotation | half map 1, unsharpened | ||||||||||||
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Density Histograms |
-Half map: half map 3, unsharpened
File | emd_21509_half_map_2.map | ||||||||||||
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Annotation | half map 3, unsharpened | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Mayaro virus-Fab CHK-265 complex
Entire | Name: Mayaro virus-Fab CHK-265 complex |
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Components |
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-Supramolecule #1: Mayaro virus-Fab CHK-265 complex
Supramolecule | Name: Mayaro virus-Fab CHK-265 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #3: Fab CHK-265
Supramolecule | Name: Fab CHK-265 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#4 |
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Source (natural) | Organism: ![]() |
-Supramolecule #2: Mayaro virus
Supramolecule | Name: Mayaro virus / type: virus / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 / NCBI-ID: 59301 / Sci species name: Mayaro virus / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: Yes / Virus empty: No |
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-Macromolecule #1: E1 glycoprotein
Macromolecule | Name: E1 glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 41.612867 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: YEHTAIIPNQ VGFPYKAHVA REGYSPLTLQ MQVIETSLEP TLNLEYITCD YKTKVPSPYV KCCGTAECRT QDKPEYKCAV FTGVYPFMW GGAYCFCDSE NTQMSEAYVE RADVCKHDHA AAYRAHTASL RAKIKVTYGT VNQTVEAYVN GDHAVTIAGT K FIFGPVST ...String: YEHTAIIPNQ VGFPYKAHVA REGYSPLTLQ MQVIETSLEP TLNLEYITCD YKTKVPSPYV KCCGTAECRT QDKPEYKCAV FTGVYPFMW GGAYCFCDSE NTQMSEAYVE RADVCKHDHA AAYRAHTASL RAKIKVTYGT VNQTVEAYVN GDHAVTIAGT K FIFGPVST PWTPFDTKIL VYKGELYNQD FPRYGAGQPG RFGDIQSRTL DSRDLYANTG LKLARPAAGN IHVPYTQTPS GF KTWQKDR DSPLNAKAPF GCIIQTNPVR AMNCAVGNIP VSMDIADSAF TRLTDAPVIS ELTCTVSTCT HSSDFGGIAV LSY KVEKSG RCDIHSHSNV AVLQEVSIET EGRSVIHFST ASASPSFVVS VCSSRATCTA KCEP UniProtKB: Structural polyprotein |
-Macromolecule #2: E2 glycoprotein
Macromolecule | Name: E2 glycoprotein / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 38.041957 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: STANHFNAYK LTRPYVAYCA DCGMGHSCHS PAMIENIQAD ATDGTLKIQF ASQIGLTKTD THDHTKIRYA EGHDIAEAAR STLKVHSSS ECTVTGTMGH FILAKCPPGE RISVSFVDSK NEHRTCRIAY HHEQRLIGRE RFTVRPHHGI ELPCTTYQLT T AETSEEID ...String: STANHFNAYK LTRPYVAYCA DCGMGHSCHS PAMIENIQAD ATDGTLKIQF ASQIGLTKTD THDHTKIRYA EGHDIAEAAR STLKVHSSS ECTVTGTMGH FILAKCPPGE RISVSFVDSK NEHRTCRIAY HHEQRLIGRE RFTVRPHHGI ELPCTTYQLT T AETSEEID MHMPPDIPDR TILSQQSGNV KITVNGRTVR YSSSCGSQAV GTTTTDKTIN SCTVDKCQAY VTSHTKWQFN SP FVPRRMQ AERKGKVHIP FPLINTTCRV PLAPEALVRS GKREATLSLH PIHPTLLSYR TFGAERVFDE QWITAQTEVT IPV PVEGVE YQWGNHKPQR FVVA UniProtKB: Structural polyprotein |
-Macromolecule #3: Fab CHK-265 heavy chain
Macromolecule | Name: Fab CHK-265 heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.743719 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QIQLVQSGRE VKNPGETVKI SCKASGYTFT EYPMLWVKQA PGKGFRWMGL IYTNTGEPTY AEEFKGRFVF SLEISASTAY LQINNLTNE DTATYFCVRD YFISLDYWGQ GTTLTVSSAK TTAPSVYPLA PVCGGTTGSS VTLGCLVKGY FPEPVTLTWN S GSLSSGVH ...String: QIQLVQSGRE VKNPGETVKI SCKASGYTFT EYPMLWVKQA PGKGFRWMGL IYTNTGEPTY AEEFKGRFVF SLEISASTAY LQINNLTNE DTATYFCVRD YFISLDYWGQ GTTLTVSSAK TTAPSVYPLA PVCGGTTGSS VTLGCLVKGY FPEPVTLTWN S GSLSSGVH TFPALLQSGL YTLSSSVTVT SNTWPSQTIT CNVAHPASST KVDKKIESRR |
-Macromolecule #4: Fab CHK-265 light chain
Macromolecule | Name: Fab CHK-265 light chain / type: protein_or_peptide / ID: 4 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 22.888404 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QAVVTQESAL TTSPGETVTL TCRSNIGAVT SSNCANWVQE KPDHFFTGLI GDTNNRRSGV PARFSGSLIG DKAALTITGA QTEDEAIYF CALWYNNLWV FGGGTKLTVL GQPKSSPSVT LFPPSSEELE TNKATLVCTI TDFYPGVVTV DWKVDGTPVT Q GMETTQPS ...String: QAVVTQESAL TTSPGETVTL TCRSNIGAVT SSNCANWVQE KPDHFFTGLI GDTNNRRSGV PARFSGSLIG DKAALTITGA QTEDEAIYF CALWYNNLWV FGGGTKLTVL GQPKSSPSVT LFPPSSEELE TNKATLVCTI TDFYPGVVTV DWKVDGTPVT Q GMETTQPS KQSNNKYMAS SYLTLTARAW ERHSSYSCQV THEGHTVEKS LSR |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 3 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: C-flat / Support film - Material: CARBON / Support film - topology: HOLEY |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 85 % / Instrument: GATAN CRYOPLUNGE 3 |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 BASE (4k x 4k) / Average electron dose: 30.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal magnification: 18000 |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Applied symmetry - Point group: I (icosahedral) / Resolution.type: BY AUTHOR / Resolution: 5.3 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: jspr / Number images used: 18410 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: PROJECTION MATCHING / Software - Name: jspr |
-Atomic model buiding 1
Refinement | Protocol: RIGID BODY FIT |
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Output model | ![]() PDB-6w1c: |