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- EMDB-33499: Complex of Echo 18 and FcRn at pH7.4 -

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Basic information

Entry
Database: EMDB / ID: EMD-33499
TitleComplex of Echo 18 and FcRn at pH7.4
Map data
Sample
  • Complex: Echovirus E18
    • Complex: FcRn
      • Protein or peptide: IgG receptor FcRn large subunit p51
    • Virus: Homo sapiens (human)
      • Protein or peptide: VP1
      • Protein or peptide: VP2
      • Protein or peptide: VP3
      • Protein or peptide: VP4
KeywordsComplex / Receptor / VIRUS
Function / homology
Function and homology information


IgG immunoglobulin transcytosis in epithelial cells mediated by FcRn immunoglobulin receptor / IgG binding / beta-2-microglobulin binding / endosome membrane / immune response / external side of plasma membrane / extracellular space
Similarity search - Function
Class I Histocompatibility antigen, domains alpha 1 and 2 / : / MHC class I-like antigen recognition-like / MHC class I-like antigen recognition-like superfamily / MHC classes I/II-like antigen recognition protein / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain ...Class I Histocompatibility antigen, domains alpha 1 and 2 / : / MHC class I-like antigen recognition-like / MHC class I-like antigen recognition-like superfamily / MHC classes I/II-like antigen recognition protein / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
IgG receptor FcRn large subunit p51
Similarity search - Component
Biological speciesEchovirus E18 / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.09 Å
AuthorsLiu CC / Qu X
Funding support China, 1 items
OrganizationGrant numberCountry
Chinese Academy of Sciences81971922 China
CitationJournal: mBio / Year: 2022
Title: Human FcRn Is a Two-in-One Attachment-Uncoating Receptor for Echovirus 18.
Authors: Xiangpeng Chen / Xiao Qu / Congcong Liu / Yong Zhang / Guigen Zhang / Pu Han / Yali Duan / Qi Li / Liang Wang / Wenjing Ruan / Peiyi Wang / Wensheng Wei / George F Gao / Xin Zhao / Zhengde Xie /
Abstract: Virus-receptor interactions determine viral host range and tissue tropism. CD55 and human neonatal Fc receptor (FcRn) were found to be the binding and uncoating receptors for some of the echovirus- ...Virus-receptor interactions determine viral host range and tissue tropism. CD55 and human neonatal Fc receptor (FcRn) were found to be the binding and uncoating receptors for some of the echovirus-related enterovirus species B serotypes in our previous study. Echovirus 18 (E18), as a member of enterovirus species B, is a significant causative agent of aseptic meningitis and viral encephalitis in children. However, it does not use CD55 as a critical host factor. We conducted CRISPR/Cas9 knockout screening to determine the receptors and entry mechanisms and identified FcRn working as a dual-function receptor for E18. Knockout of and , which encode the two subunits of FcRn, prevented infection by E18 and other echoviruses in the same physiological cluster. We then elucidated the underlying molecular mechanism of receptor recognition by E18 using cryogenic electron microscopy. The binding of the FCGRT subunit to the canyon region rotates the residues around the pocket, triggering the release of the pocket factor as observed for other enterovirus species B members. E18 is a member of enterovirus species B. As one of the most common enterovirus serotypes in nonpolio enterovirus detection, it easily infects children and causes various clinical symptoms. Aseptic meningitis and viral encephalitis are the most commonly reported syndromes associated with E18. No effective antiviral drugs or approved vaccines are available. Previous studies showed that CD55 and FcRn were the binding and uncoating receptors for some echoviruses. However, we found that CD55 is not the critical host factor for E18. Thus, we want to determine the receptors and elucidate the entry mechanism of E18. Our findings reveal that FcRn is a two-in-one attachment-uncoating receptor for E18.
History
DepositionMay 29, 2022-
Header (metadata) releaseJun 29, 2022-
Map releaseJun 29, 2022-
UpdateJul 3, 2024-
Current statusJul 3, 2024Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_33499.map.gz / Format: CCP4 / Size: 307.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.01 Å/pix.
x 432 pix.
= 436.32 Å
1.01 Å/pix.
x 432 pix.
= 436.32 Å
1.01 Å/pix.
x 432 pix.
= 436.32 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.01 Å
Density
Contour LevelBy AUTHOR: 0.02
Minimum - Maximum-0.119299114 - 0.17838119
Average (Standard dev.)0.0009836457 (±0.011002492)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin-216-216-216
Dimensions432432432
Spacing432432432
CellA=B=C: 436.32 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_33499_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_33499_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_33499_half_map_2.map
Projections & Slices
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Projections

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Density Histograms

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Sample components

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Entire : Echovirus E18

EntireName: Echovirus E18
Components
  • Complex: Echovirus E18
    • Complex: FcRn
      • Protein or peptide: IgG receptor FcRn large subunit p51
    • Virus: Homo sapiens (human)
      • Protein or peptide: VP1
      • Protein or peptide: VP2
      • Protein or peptide: VP3
      • Protein or peptide: VP4

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Supramolecule #1: Echovirus E18

SupramoleculeName: Echovirus E18 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Echovirus E18

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Supramolecule #3: FcRn

SupramoleculeName: FcRn / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2

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Supramolecule #2: Homo sapiens

SupramoleculeName: Homo sapiens / type: virus / ID: 2 / Parent: 1 / Macromolecule list: #1, #3-#5 / NCBI-ID: 9606 / Sci species name: Homo sapiens / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: Yes / Virus empty: No

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Macromolecule #1: VP1

MacromoleculeName: VP1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Echovirus E18
Molecular weightTheoretical: 35.113328 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GDNQDRTVAN TQPSGPSNSK EIPALTAVET GHTSQVDPSD TLQTRHVVNF HSRSESTVEN FMGRAACVFM DQYKLNGEET STDNFAVWT INVREMAQLR RKCELFTYMR FDIEMTMVIT SCQDQGTQLE QDMPVLTHQI MYVPPGGPIP AKVDSYEWQT S TNPSVFWT ...String:
GDNQDRTVAN TQPSGPSNSK EIPALTAVET GHTSQVDPSD TLQTRHVVNF HSRSESTVEN FMGRAACVFM DQYKLNGEET STDNFAVWT INVREMAQLR RKCELFTYMR FDIEMTMVIT SCQDQGTQLE QDMPVLTHQI MYVPPGGPIP AKVDSYEWQT S TNPSVFWT EGNAPARMSI PFISVGNAYS LFYDGWSHFT QDGTYGYTTL NAMGKLFVRH VNKSSPHQIT STIRVYFKPK HI KAWVPRP PRLCPYINKG DVNFVVTEVT DARKSITDTP HPEHSVLVTR GAFGQQSGAA YIGNYKVVNR HLATH

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Macromolecule #2: IgG receptor FcRn large subunit p51

MacromoleculeName: IgG receptor FcRn large subunit p51 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 29.294971 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: LSLLYHLTAV SSPAPGTPAF WVSGWLGPQQ YLSYNSLRGE AEPCGAWVWE NQVSWYWEKE TTDLRIKEKL FLEAFKALGG KGPYTLQGL LGCELGPDNT SVPTAKFALN GEEFMNFDLK QGTWGGDWPE ALAISQRWQQ QDKAANKELT FLLFSCPHRL R EHLERGRG ...String:
LSLLYHLTAV SSPAPGTPAF WVSGWLGPQQ YLSYNSLRGE AEPCGAWVWE NQVSWYWEKE TTDLRIKEKL FLEAFKALGG KGPYTLQGL LGCELGPDNT SVPTAKFALN GEEFMNFDLK QGTWGGDWPE ALAISQRWQQ QDKAANKELT FLLFSCPHRL R EHLERGRG NLEWKEPPSM RLKARPSSPG FSVLTCSAFS FYPPELQLRF LRNGLAAGTG QGDFGPNSDG SFHASSSLTV KS GDEHHYC CIVQHAGLAQ PLRVEL

UniProtKB: IgG receptor FcRn large subunit p51

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Macromolecule #3: VP2

MacromoleculeName: VP2 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Echovirus E18
Molecular weightTheoretical: 28.805348 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SPSAEECGYS DRVRSMTLGN STITTQESAN VVVGYGEWPS YLSDKEATAE DQPTQPDVAT CRFYTLESVQ WEKSSPGWWW KFPEALKNM GLFGQNMHYH YLGRAGYTIH VQCNASKFHQ GCLLVVCVPE AEMGCADTST TFPATELTTE EEPHVFTSDS I TGKKVQAA ...String:
SPSAEECGYS DRVRSMTLGN STITTQESAN VVVGYGEWPS YLSDKEATAE DQPTQPDVAT CRFYTLESVQ WEKSSPGWWW KFPEALKNM GLFGQNMHYH YLGRAGYTIH VQCNASKFHQ GCLLVVCVPE AEMGCADTST TFPATELTTE EEPHVFTSDS I TGKKVQAA VCNAGMGVGV GNLTIFPHQW INLRTNNSAT IVMPYINSVP MDNMFRHYNF TLMIIPFAPL NFNEGATAYV PV TVTIAPM YAEYNGLRLA STQ

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Macromolecule #4: VP3

MacromoleculeName: VP3 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Echovirus E18
Molecular weightTheoretical: 26.134842 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GVPVLNTPGS TQFLTSDDFQ SPSAMPQFDE TPEMHIPGEV RNLMEMAEVD SVVPVNNITG KTKSMEAYQI AVGTGNTDKT KPIFSFQMD PGYSSVLKRT LLGEMLNYYA HWSGSVKLTF LFCGSAMATG KLLISYSPPG ASVPSSRKDA MLGTHIIWDI G LQSSCVLC ...String:
GVPVLNTPGS TQFLTSDDFQ SPSAMPQFDE TPEMHIPGEV RNLMEMAEVD SVVPVNNITG KTKSMEAYQI AVGTGNTDKT KPIFSFQMD PGYSSVLKRT LLGEMLNYYA HWSGSVKLTF LFCGSAMATG KLLISYSPPG ASVPSSRKDA MLGTHIIWDI G LQSSCVLC VPWISQSHYR MVQQDPYTSA GYITCWYQTN IVVPPGAPTS CDVLCFASAC NDFSVRLLRD TPFMAQPGKL Q

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Macromolecule #5: VP4

MacromoleculeName: VP4 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Echovirus E18
Molecular weightTheoretical: 7.502346 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
MGAQVSTQKT GAHETSLNAK GNSIIHYTNI NFYKDAASSA SNRQELQQDP GKFTDPVKDL MVKTLPALN

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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

Concentration3 mg/mL
BufferpH: 7.4
GridModel: EMS Lacey Carbon / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 2 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. / Pretreatment - Atmosphere: AIR
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV
Details: blot for 3 seconds and wait for 3 seconds before plunging.

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Electron microscopy

MicroscopeFEI TITAN KRIOS
TemperatureMin: 80.0 K / Max: 80.0 K
Alignment procedureComa free - Residual tilt: 100.0 mrad
Specialist opticsEnergy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Dimensions - Width: 3838 pixel / Digitization - Dimensions - Height: 3710 pixel / Digitization - Frames/image: 1-40 / Number grids imaged: 1 / Number real images: 2028 / Average exposure time: 0.088 sec. / Average electron dose: 1.025 e/Å2 / Details: Images were collected in super-resolution mode.
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 70.0 µm / Calibrated defocus max: 3.5 µm / Calibrated defocus min: 1.5 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.5 µm / Nominal defocus min: 1.5 µm / Nominal magnification: 59000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 23904
Startup modelType of model: NONE
Final reconstructionNumber classes used: 1 / Applied symmetry - Point group: I (icosahedral) / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 3.09 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.0.8) / Number images used: 23904
Initial angle assignmentType: ANGULAR RECONSTITUTION / Software - Name: RELION (ver. 3.0.8)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 3.0.8)
Final 3D classificationNumber classes: 8 / Software - Name: RELION (ver. 3.0.8)
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial model
PDB IDChain

chain_id: A, source_name: PDB, initial_model_type: experimental model

chain_id: B, source_name: PDB, initial_model_type: experimental model

chain_id: C, source_name: PDB, initial_model_type: experimental model

chain_id: D, source_name: PDB, initial_model_type: experimental model
RefinementSpace: REAL / Protocol: RIGID BODY FIT
Output model

PDB-7xxa:
Complex of Echo 18 and FcRn at pH7.4

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