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- EMDB-27271: CryoEM structure of Western equine encephalitis virus VLP in comp... -

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Basic information

Entry
Database: EMDB / ID: EMD-27271
TitleCryoEM structure of Western equine encephalitis virus VLP in complex with the avian MXRA8 receptor
Map dataMap of WEEV-VLP bound to MXRA8 asymmetric unit.
Sample
  • Complex: Western equine encephalitis virus VLP in complex with avian MXRA8 receptor
    • Protein or peptide: E1 envelope glycoprotein
    • Protein or peptide: E2 envelope glycoprotein
    • Protein or peptide: Matrix remodeling-associated protein 8
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsWEEV / MXRA8 / Receptor / Alphavirus / Avian / VLP / Structural Genomics / PSI-2 / Protein Structure Initiative / Center for Structural Genomics of Infectious Diseases / CSGID / VIRUS LIKE PARTICLE
Function / homology
Function and homology information


T=4 icosahedral viral capsid / host cell cytoplasm / cell differentiation / cell adhesion / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / symbiont entry into host cell / virion attachment to host cell / host cell nucleus / host cell plasma membrane ...T=4 icosahedral viral capsid / host cell cytoplasm / cell differentiation / cell adhesion / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / symbiont entry into host cell / virion attachment to host cell / host cell nucleus / host cell plasma membrane / virion membrane / structural molecule activity / cell surface / proteolysis / membrane / plasma membrane
Similarity search - Function
Matrix remodeling-associated protein 8 / Alphavirus E2 glycoprotein, domain B / Peptidase S3, togavirin / Alphavirus E2 glycoprotein / Alphavirus E3 spike glycoprotein / Alphavirus E1 glycoprotein / Alphavirus E2 glycoprotein, domain A / Alphavirus E2 glycoprotein, domain C / Alphavirus E2 glycoprotein / Alphavirus core protein ...Matrix remodeling-associated protein 8 / Alphavirus E2 glycoprotein, domain B / Peptidase S3, togavirin / Alphavirus E2 glycoprotein / Alphavirus E3 spike glycoprotein / Alphavirus E1 glycoprotein / Alphavirus E2 glycoprotein, domain A / Alphavirus E2 glycoprotein, domain C / Alphavirus E2 glycoprotein / Alphavirus core protein / Alphavirus E3 glycoprotein / Alphavirus E1 glycoprotein / Alphavirus core protein (CP) domain profile. / Flavivirus/Alphavirus glycoprotein, immunoglobulin-like domain superfamily / Flavivirus glycoprotein, central and dimerisation domain superfamily / Flaviviral glycoprotein E, dimerisation domain / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin subtype / Immunoglobulin / Immunoglobulin E-set / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan
Similarity search - Domain/homology
Matrix remodeling-associated protein 8 / Structural polyprotein
Similarity search - Component
Biological speciesWestern equine encephalitis virus / Asarcornis scutulata (bird)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.74 Å
AuthorsZimmerman MI / Fremont DH
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)HHSN272201700060C United States
CitationJournal: Cell / Year: 2023
Title: Vertebrate-class-specific binding modes of the alphavirus receptor MXRA8.
Authors: Ofer Zimmerman / Maxwell I Zimmerman / Saravanan Raju / Christopher A Nelson / John M Errico / Emily A Madden / Autumn C Holmes / Ahmed O Hassan / Laura A VanBlargan / Arthur S Kim / Lucas J ...Authors: Ofer Zimmerman / Maxwell I Zimmerman / Saravanan Raju / Christopher A Nelson / John M Errico / Emily A Madden / Autumn C Holmes / Ahmed O Hassan / Laura A VanBlargan / Arthur S Kim / Lucas J Adams / Katherine Basore / Bradley M Whitener / Sathvik Palakurty / Hannah G Davis-Adams / Chengqun Sun / Theron Gilliland / James T Earnest / Hongming Ma / Gregory D Ebel / Christian Zmasek / Richard H Scheuermann / William B Klimstra / Daved H Fremont / Michael S Diamond /
Abstract: MXRA8 is a receptor for chikungunya (CHIKV) and other arthritogenic alphaviruses with mammalian hosts. However, mammalian MXRA8 does not bind to alphaviruses that infect humans and have avian ...MXRA8 is a receptor for chikungunya (CHIKV) and other arthritogenic alphaviruses with mammalian hosts. However, mammalian MXRA8 does not bind to alphaviruses that infect humans and have avian reservoirs. Here, we show that avian, but not mammalian, MXRA8 can act as a receptor for Sindbis, western equine encephalitis (WEEV), and related alphaviruses with avian reservoirs. Structural analysis of duck MXRA8 complexed with WEEV reveals an inverted binding mode compared with mammalian MXRA8 bound to CHIKV. Whereas both domains of mammalian MXRA8 bind CHIKV E1 and E2, only domain 1 of avian MXRA8 engages WEEV E1, and no appreciable contacts are made with WEEV E2. Using these results, we generated a chimeric avian-mammalian MXRA8 decoy-receptor that neutralizes infection of multiple alphaviruses from distinct antigenic groups in vitro and in vivo. Thus, different alphaviruses can bind MXRA8 encoded by different vertebrate classes with distinct engagement modes, which enables development of broad-spectrum inhibitors.
History
DepositionJun 13, 2022-
Header (metadata) releaseDec 20, 2023-
Map releaseDec 20, 2023-
UpdateSep 24, 2025-
Current statusSep 24, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_27271.png

Downloads & links

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Map

FileDownload / File: emd_27271.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationMap of WEEV-VLP bound to MXRA8 asymmetric unit.
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.2 Å/pix.
x 280 pix.
= 336. Å		1.2 Å/pix.
x 280 pix.
= 336. Å		1.2 Å/pix.
x 280 pix.
= 336. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.2 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.35
Minimum - Maximum-1.5052977 - 2.582493
Average (Standard dev.)0.0038370634 (±0.06680423)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions280280280
Spacing280280280
CellA=B=C: 336.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: Half-map A

Fileemd_27271_half_map_1.map
AnnotationHalf-map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half-map B

Fileemd_27271_half_map_2.map
AnnotationHalf-map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Western equine encephalitis virus VLP in complex with avian MXRA8...

EntireName: Western equine encephalitis virus VLP in complex with avian MXRA8 receptor
Components
  • Complex: Western equine encephalitis virus VLP in complex with avian MXRA8 receptor
    • Protein or peptide: E1 envelope glycoprotein
    • Protein or peptide: E2 envelope glycoprotein
    • Protein or peptide: Matrix remodeling-associated protein 8
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Western equine encephalitis virus VLP in complex with avian MXRA8...

SupramoleculeName: Western equine encephalitis virus VLP in complex with avian MXRA8 receptor
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Western equine encephalitis virus
Molecular weightTheoretical: 495 kDa/nm

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Macromolecule #1: E1 envelope glycoprotein

MacromoleculeName: E1 envelope glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Western equine encephalitis virus
Molecular weightTheoretical: 47.188562 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: FEHATTVPNV PGIPYKALVE RAGYAPLNLE ITVVSSELTP STNKEYVTCK FHTVVPSPQV KCCGSLECKA SSKADYTCRV FGGVYPFMW GGAQCFCDSE NTQLSEAYVE FAPDCTIDHA VALKVHTAAL KVGLRIVYGN TTARLDTFVN GVTPGSSRDL K VIAGPISA ...String:
FEHATTVPNV PGIPYKALVE RAGYAPLNLE ITVVSSELTP STNKEYVTCK FHTVVPSPQV KCCGSLECKA SSKADYTCRV FGGVYPFMW GGAQCFCDSE NTQLSEAYVE FAPDCTIDHA VALKVHTAAL KVGLRIVYGN TTARLDTFVN GVTPGSSRDL K VIAGPISA AFSPFDHKVV IRKGLVYNYD FPEYGAMNPG AFGDIQASSL DATDIVARTD IRLLKPSVKN IHVPYTQAVS GY EMWKNNS GRPLQETAPF GCKIEVEPLR ATNCAYGHIP ISIDIPDAAF VRSSESPTIL EVSCTVADCI YSADFGGSLT LQY KANREG HCPVHSHSTT AVLKEATTHV TATGSITLHF STSSPQANFI VSLCGKKTTC NAECKPPADH IIGEPHKVDQ EFQA AVSKT SWNWLLALFG GASSLIVVGL IVLVCSSMLI NTR

UniProtKB: Structural polyprotein

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Macromolecule #2: E2 envelope glycoprotein

MacromoleculeName: E2 envelope glycoprotein / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Western equine encephalitis virus
Molecular weightTheoretical: 46.171617 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: ITDDFTLTSP YLGFCPYCRH SAPCFSPIKI ENVWDESDDG SIRIQVSAQF GYNQAGTADV TKFRYMSYDH DHDIKEDSME KLAISTSGP CRRLGHKGYF LLAQCPPGDS VTVSITSGAS ENSCTVEKKI RRKFVGREEY LFPPVHGKLV KCHVYDHLKE T SAGYITMH ...String:
ITDDFTLTSP YLGFCPYCRH SAPCFSPIKI ENVWDESDDG SIRIQVSAQF GYNQAGTADV TKFRYMSYDH DHDIKEDSME KLAISTSGP CRRLGHKGYF LLAQCPPGDS VTVSITSGAS ENSCTVEKKI RRKFVGREEY LFPPVHGKLV KCHVYDHLKE T SAGYITMH RPGPHAYKSY LEEASGEVYI KPPSGKNVTY ECKCGDYSTG IVSTRTKMNG CTKAKQCIAY KRDQTKWVFN SP DLIRHTD HSVQGKLHIP FRLTPTVCPV PLAHTPTVTK WFKGITLHLT ATRPTLLTTR KLGLRADATA EWITGTTSRN FSV GREGLE YVWGNHEPVR VWAQESAPGD PHGWPHEIII HYYHRHPVYT VIVLCGVALA ILVGTASSAA CIAKARRDCL TPYA LAPNA TVPTALAVLC

UniProtKB: Structural polyprotein

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Macromolecule #3: Matrix remodeling-associated protein 8

MacromoleculeName: Matrix remodeling-associated protein 8 / type: protein_or_peptide / ID: 3 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Asarcornis scutulata (bird)
Molecular weightTheoretical: 30.615361 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: NSVVVSVLNI SATLGSQAVL PCKSYRMVWT QDRLNDRQRV VHWDVYSTYY GDNKMERLCD MYSAGDQRVY SSYNQGRIFM PQNAFTDGN FSLVIKDVAE SDGGIYSCNL HHHYCHLYET VKIQLDVTKK AKAAKEYWDG EKAVIVALEG STVMLPCVNR N QIWTERHS ...String:
NSVVVSVLNI SATLGSQAVL PCKSYRMVWT QDRLNDRQRV VHWDVYSTYY GDNKMERLCD MYSAGDQRVY SSYNQGRIFM PQNAFTDGN FSLVIKDVAE SDGGIYSCNL HHHYCHLYET VKIQLDVTKK AKAAKEYWDG EKAVIVALEG STVMLPCVNR N QIWTERHS EEEQQVVHWD RQPPGVPHDR ADRLIDLYAS GERRSYGPLF IRQKMNITDT AFALGDFSLR ISELESADEG TY SCHLHHH YCGLHERRIY QVFVTEPV

UniProtKB: Matrix remodeling-associated protein 8

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Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 12 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

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

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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: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 1.03 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.5 µm

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Image processing

CTF correctionType: PHASE FLIPPING ONLY
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.74 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 250347
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: ANGULAR RECONSTITUTION

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