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- EMDB-46709: Molecular basis of pathogenicity of the recently emerged FCoV-23 ... -

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Basic information

Entry
Database: EMDB / ID: EMD-46709
TitleMolecular basis of pathogenicity of the recently emerged FCoV-23 coronavirus. FCoV-23 S short
Map dataMain map
Sample
  • Complex: FCoV-23 S short
    • Protein or peptide: Spike glycoprotein
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: PALMITOLEIC ACID
  • Ligand: water
KeywordsCoronavirus / alphacoronavirus / feline coronavirus / cryo-EM / neutralization assays / binding assays / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / VIRAL PROTEIN
Biological speciesFeline coronavirus
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-
UpdateJul 23, 2025-
Current statusJul 23, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_46709.png

Downloads & links

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Map

FileDownload / File: emd_46709.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationMain map
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
1 Å/pix.
x 512 pix.
= 512. Å		1 Å/pix.
x 512 pix.
= 512. Å		1 Å/pix.
x 512 pix.
= 512. Å

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.585
Minimum - Maximum-2.2012455 - 3.7992015
Average (Standard dev.)0.00023876474 (±0.06386935)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 512.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: Unsharpened map

Fileemd_46709_additional_1.map
AnnotationUnsharpened map
Projections & Slices
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Half map: half map A

Fileemd_46709_half_map_1.map
Annotationhalf map A
Projections & Slices
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Histogram

Histogram (log scale)

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Half map: half map B

Fileemd_46709_half_map_2.map
Annotationhalf map B
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Sample components

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Entire : FCoV-23 S short

EntireName: FCoV-23 S short
Components
  • Complex: FCoV-23 S short
    • Protein or peptide: Spike glycoprotein
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: PALMITOLEIC ACID
  • Ligand: water

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Supramolecule #1: FCoV-23 S short

SupramoleculeName: FCoV-23 S short / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Feline coronavirus

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Macromolecule #1: Spike glycoprotein

MacromoleculeName: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Feline coronavirus / Strain: FCoV-23
Molecular weightTheoretical: 138.283875 KDa
Recombinant expressionOrganism: Mammalia (mammals)
SequenceString: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTIKPNNDCR QVNVTQLDGN ENLIRDFLFQ NFKEEGTNVF APTVGGYIPD GFSFNNWFL LTNDSTFVSG RFVTNQPLLV NCLWPVPSFG VAAQEFCFEG AQFSQCNGVS LNNTVDVIRF NLNFTADVQS G MGATVFSL ...String:
MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTIKPNNDCR QVNVTQLDGN ENLIRDFLFQ NFKEEGTNVF APTVGGYIPD GFSFNNWFL LTNDSTFVSG RFVTNQPLLV NCLWPVPSFG VAAQEFCFEG AQFSQCNGVS LNNTVDVIRF NLNFTADVQS G MGATVFSL NTTGGVILEI SCYNDTVRES SFYSYGEIPF GITDGPKYCY VLYNGTALKY LGTLPPSVKE IAISKWGHFY IN GYNFFST FPIDCISFNL TTSTSGAFWT IAYTSYTEAL VQVENTAIKK VTYCNSHINN IKCSQLTANL QNGFYPVASS EVG LVNKSV VLLPSFYSHT SVNITIDLGM KLSGYGQPIA SALSNITLPM QDNNTDVYCI RSNQFSVYVH STCKSSLWDN VFNS DCTDV LHATAVIKTG TCPFSFDKLN NYLTFNKFCL SLHPVGANCK FDVAARTRTN EQVVRSLYVI YEEGDNIAGV PSDNS GLHD LSVLHLDSCT DYNIYGKTGI GIIRQTNSTL LSGLYYTSLS GDLLGFKNVT DGVVYSVTPC DVSAQAAVID GTIVGA MTS INSELLGLTH WTTTPNFYYY SIYNYTNERT RGTAIDSNDV DCEPIITYSN IGVCKNGALV FINVTHSDGD VQPISTG NV TIPTNFTISV QVEYIQVYTT PVSIDCSRYV CNGNPRCNKL LTQYVSACQT IEQALAMGAR LENMEVDSML FVSENALK L ASVEAFNSTE HLDPIYKEWP NIGGSWLGGL KDILPSHNSK RKYRSAIEDL LFDKVVTSGL GTVDEDYKRC TGGYDIADL VCAQYYNGIM VLPGVANDDK MTMYTASLAG GITLGALGGG AVAIPFAVAV QARLNYVALQ TDVLNKNQQI LANAFNQAIG NITQAFGKV NDAIHQTSKG LATVAKALAK VQDVVNTQGQ ALSHLTVQLQ NNFQAISSSI SDIYNRLDPP SADAQVDRLI T GRLTALNA FVSQTLTRQA EVRASRQLAK DKVNECVRSQ SQRFGFCGNG THLFSLANAA PNGMIFFHTV LLPTAYETVT AW SGICASD GDHTFGLVVK DVQLTLFRNL DDKFYLTPRT MYQPRVATIS DFVQIEGCDV LFVNATVIEL PGIIPDYIDI NQT VQDILE NYRPNWTVPE LTLDIFNSTY LNLTGEINDL EFRSEKLHNT TVELAVLIDN INNTLVNLEW LNRIETYVKS GGYI PEAPR DGQAYVRKDG EWVLLSTFLV PRGSGGSGGS GLNDIFEAQK IEWHEGGSHH HHHHHH

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Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 21 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

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

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Macromolecule #7: PALMITOLEIC ACID

MacromoleculeName: PALMITOLEIC ACID / type: ligand / ID: 7 / Number of copies: 6 / Formula: PAM
Molecular weightTheoretical: 254.408 Da
Chemical component information

ChemComp-PAM:
PALMITOLEIC ACID

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Macromolecule #8: water

MacromoleculeName: water / type: ligand / ID: 8 / Number of copies: 141 / 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: 262922
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING

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