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- EMDB-46708: Molecular basis of pathogenicity of the recently emerged FCoV-23 ... -

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Basic information

Entry
Database: EMDB / ID: EMD-46708
TitleMolecular basis of pathogenicity of the recently emerged FCoV-23 coronavirus. Complex of fAPN with FCoV-23 RBD
Map datamain map
Sample
  • Complex: FCoV-23 S RBD in complex with feline APN
    • Protein or peptide: Aminopeptidase N,Immunoglobulin gamma-1 heavy chain
    • Protein or peptide: Spike glycoprotein
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: ZINC ION
  • Ligand: water
KeywordsCoronavirus / alphacoronavirus / feline coronavirus / cryo-EM / neutralization assays / binding assays / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / VIRAL PROTEIN-HYDROLASE complex
Function / homology
Function and homology information


alanyl aminopeptidase activity / membrane alanyl aminopeptidase / peptide catabolic process / metalloaminopeptidase activity / immunoglobulin complex / peptide binding / virus receptor activity / angiogenesis / adaptive immune response / cell differentiation ...alanyl aminopeptidase activity / membrane alanyl aminopeptidase / peptide catabolic process / metalloaminopeptidase activity / immunoglobulin complex / peptide binding / virus receptor activity / angiogenesis / adaptive immune response / cell differentiation / proteolysis / extracellular space / extracellular region / zinc ion binding / plasma membrane / cytoplasm
Similarity search - Function
Aminopeptidase N-type / ERAP1-like C-terminal domain / : / ERAP1-like C-terminal domain / Peptidase M1, alanine aminopeptidase/leukotriene A4 hydrolase / Peptidase M1, membrane alanine aminopeptidase / Aminopeptidase N-like , N-terminal domain / Peptidase family M1 domain / Peptidase M1 N-terminal domain / Aminopeptidase N-like , N-terminal domain superfamliy ...Aminopeptidase N-type / ERAP1-like C-terminal domain / : / ERAP1-like C-terminal domain / Peptidase M1, alanine aminopeptidase/leukotriene A4 hydrolase / Peptidase M1, membrane alanine aminopeptidase / Aminopeptidase N-like , N-terminal domain / Peptidase family M1 domain / Peptidase M1 N-terminal domain / Aminopeptidase N-like , N-terminal domain superfamliy / Peptidase M4/M1, CTD superfamily / : / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Neutral zinc metallopeptidases, zinc-binding region signature. / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin subtype / Immunoglobulin / 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
Immunoglobulin gamma-1 heavy chain / Aminopeptidase N
Similarity search - Component
Biological speciesFeline coronavirus / Felis catus (domestic cat)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.5 Å
AuthorsTortorici MA / Veesler D / Seattle Structural Genomics Center for Infectious Disease (SSGCID)
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI158186 United States
CitationJournal: Nature / Year: 2025
Title: Loss of FCoV-23 spike domain 0 enhances fusogenicity and entry kinetics.
Authors: M Alejandra Tortorici / Annette Choi / Cecily A Gibson / Jimin Lee / Jack T Brown / Cameron Stewart / Anshu Joshi / Sheri Harari / Isabelle Willoughby / Catherine Treichel / Elizabeth M Leaf ...Authors: M Alejandra Tortorici / Annette Choi / Cecily A Gibson / Jimin Lee / Jack T Brown / Cameron Stewart / Anshu Joshi / Sheri Harari / Isabelle Willoughby / Catherine Treichel / Elizabeth M Leaf / Jesse D Bloom / Neil P King / Christine Tait-Burkard / Gary R Whittaker / David Veesler /
Abstract: The ability of coronaviruses to recombine and cross species barriers affects human and animal health globally and is a pandemic threat. FCoV-23 is a recently emerged, highly pathogenic recombinant ...The ability of coronaviruses to recombine and cross species barriers affects human and animal health globally and is a pandemic threat. FCoV-23 is a recently emerged, highly pathogenic recombinant coronavirus responsible for a widespread outbreak of feline infectious peritonitis. Here we report cryogenic electron microscopy structures of two FCoV-23 spike isoforms that correspond to the in-host loss of domain 0 observed in clinical samples. The loss of domain 0 markedly enhances the fusogenicity and kinetics of entry into cells and possibly enables biotype switching and lethality. We show that FCoV-23 can use several aminopeptidase N orthologues as receptors and reveal the molecular determinants of receptor species tropism, including a glycan that modulates human receptor engagement. We define antigenic relationships among alphacoronaviruses that infect humans and other mammalian species and identify a cross-reactive alphacoronavirus monoclonal antibody that inhibits FCoV-23 entry. Our results pave the way for the development of vaccines and therapeutics that target this highly pathogenic virus.
History
DepositionAug 23, 2024-
Header (metadata) releaseJul 9, 2025-
Map releaseJul 9, 2025-
UpdateSep 17, 2025-
Current statusSep 17, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_46708.png

Downloads & links

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Map

FileDownload / File: emd_46708.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationmain map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.01 Å/pix.
x 512 pix.
= 515.891 Å		1.01 Å/pix.
x 512 pix.
= 515.891 Å		1.01 Å/pix.
x 512 pix.
= 515.891 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.0076 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.6
Minimum - Maximum-3.6692743 - 5.32125
Average (Standard dev.)-0.0002664625 (±0.055212356)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 515.8912 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: Unsharpened map

Fileemd_46708_additional_1.map
AnnotationUnsharpened map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map A

Fileemd_46708_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_46708_half_map_2.map
Annotationhalf map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
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Histogram

Histogram (log scale)

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Sample components

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Entire : FCoV-23 S RBD in complex with feline APN

EntireName: FCoV-23 S RBD in complex with feline APN
Components
  • Complex: FCoV-23 S RBD in complex with feline APN
    • Protein or peptide: Aminopeptidase N,Immunoglobulin gamma-1 heavy chain
    • Protein or peptide: Spike glycoprotein
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: ZINC ION
  • Ligand: water

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Supramolecule #1: FCoV-23 S RBD in complex with feline APN

SupramoleculeName: FCoV-23 S RBD in complex with feline APN / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Feline coronavirus

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Macromolecule #1: Aminopeptidase N,Immunoglobulin gamma-1 heavy chain

MacromoleculeName: Aminopeptidase N,Immunoglobulin gamma-1 heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: membrane alanyl aminopeptidase
Source (natural)Organism: Felis catus (domestic cat)
Molecular weightTheoretical: 133.824047 KDa
Recombinant expressionOrganism: Mammalia (mammals)
SequenceString: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTDQSKPWNV YRLPKTLIPD SYNVTLRPYL TPNNKGLYVF TGTNIVRFTC KESTNIVII HSKRLNYTSH QGHMVALSGV GGFHPQPVIV RTELVELTEY LVVHLQEPLV AGRQYEMNSE FQGELADDLA G FYRSEYME ...String:
MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTDQSKPWNV YRLPKTLIPD SYNVTLRPYL TPNNKGLYVF TGTNIVRFTC KESTNIVII HSKRLNYTSH QGHMVALSGV GGFHPQPVIV RTELVELTEY LVVHLQEPLV AGRQYEMNSE FQGELADDLA G FYRSEYME NGVKKVLATT HMQATEARKS FPCFDEPAMK ATFNITIIHP NNLVALSNML PRGPSVPFGE DPTWKVTEFE TT PIMSTYL LAYIVSEFSY VETRAPSGVL IRIWARPSAI NQGHGDYALK VTGPILDFFS QHYDTPYPLN KSDQIALPDF NAG AMENWG LVTYRESALL YDRQSSSSGN QERVVTVIAH ELAHQWFGNL VTLEWWNDLW LNEGFASYVE YLGADFAEPT WNLK DLMVL NDVYRVMAVD ALASSHPLST PASEINTPAQ ISEVFDSISY SKGASVLRML SNFLTEDLFK MGIASYLHTY KYGNT IYLN LWEHLQQVVD KQPTIKLPDT VSAIMDRWIL QMGFPVITVD TQTGTISQQH FLLDPQSVVT RPSQFNYLWI VPISSV RSG SPQAHYWLPG VEKAQNDLFK TTANDWVLLN LNVTGYYLVN YDNENWKKIQ TQLQTDLSVI PVINRAQVIH DAFNLAS AQ KVPVTLALNN TLFLIQETEY MPWQAALSSL SYFKLMFDRS EVYGPMKRYL KKQVTPLFNH FERVTKNWTD HPQTLMDQ Y SEINAVSTAC SYGVPECEKL AATLFAQWKK NPQNNPIHPN LRSTVYCNAI AQGGEEEWNF VWEQFLKAEL VNEADKLRG ALACSNQVWI LNRFLSYTLD PNLIRKQDVT STLSSISSNV VGQTLVWDFV QSNWKKLFQD YGTGSFSFSN LIQAVTRRFS TEFELQQLE QFKKNNMDTG FGSATRALEQ ALEKTKANLK WVKENKDVVL RWFTENSGGS LVPRGSGSGS GDPEPKSCDK T HTCPPCPA PELLGGPSVF LFPPKPKDTL MISRTPEVTC VVVDVSHEDP EVKFNWYVDG VEVHNAKTKP REEQYNSTYR VV SVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT LPPSRDELTK NQVSLTCLVK GFYPSDIAVE WES NGQPEN NYKTTPPVLD SDGSFFLYSK LTVDKSRWQQ GNVFSCSVMH EALHNHYTQK SLSLSPGK

UniProtKB: Aminopeptidase N, Immunoglobulin gamma-1 heavy chain

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Macromolecule #2: Spike glycoprotein

MacromoleculeName: Spike glycoprotein / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Feline coronavirus / Strain: FCoV-23
Molecular weightTheoretical: 23.214062 KDa
Recombinant expressionOrganism: Mammalia (mammals)
SequenceString: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTSFYSHTSV NITIDLGMKL SGYGQPIASA LSNITLPMQD NNTDVYCIRS NQFSVYVHS TCKSSLWDNV FNSDCTDVLH ATAVIKTGTC PFSFDKLNNY LTFNKFCLSL HPVGANCKFD VAARTRTNEQ V VRSLYVIY ...String:
MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTSFYSHTSV NITIDLGMKL SGYGQPIASA LSNITLPMQD NNTDVYCIRS NQFSVYVHS TCKSSLWDNV FNSDCTDVLH ATAVIKTGTC PFSFDKLNNY LTFNKFCLSL HPVGANCKFD VAARTRTNEQ V VRSLYVIY EEGDNIAGVP SDNGSSGGSG LNDIFEAQKI EWHEGGSHHH HHHHH

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Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 2 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

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

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Macromolecule #6: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 6 / Number of copies: 2 / Formula: ZN
Molecular weightTheoretical: 65.409 Da

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Macromolecule #7: water

MacromoleculeName: water / type: ligand / ID: 7 / Number of copies: 220 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

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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 KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 466950
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING

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