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- EMDB-46739: Molecular basis of pathogenicity of the recently emerged FCoV-23 ... -

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Basic information

Entry
Database: EMDB / ID: EMD-46739
TitleMolecular basis of pathogenicity of the recently emerged FCoV-23 coronavirus. FCoV-23 S long with Do in mixed conformations (global refinement).
Map datamain map
Sample
  • Complex: FCoV-23 S long with Do in mixed conformations (global refinement)
    • 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: 2.7 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 24, 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_46739.png

Downloads & links

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Map

FileDownload / File: emd_46739.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.)
1.01 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

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Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.0076 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.331
Minimum - Maximum-2.0317447 - 3.8140914
Average (Standard dev.)-0.00016133986 (±0.062489923)
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_46739_additional_1.map
AnnotationUnsharpened map
Projections & Slices
AxesZYX

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Half map: Half map A

Fileemd_46739_half_map_1.map
AnnotationHalf map A
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Histogram

Histogram (log scale)

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Half map: Half map B

Fileemd_46739_half_map_2.map
AnnotationHalf map B
Projections & Slices
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Sample components

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Entire : FCoV-23 S long with Do in mixed conformations (global refinement)

EntireName: FCoV-23 S long with Do in mixed conformations (global refinement)
Components
  • Complex: FCoV-23 S long with Do in mixed conformations (global refinement)
    • 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 long with Do in mixed conformations (global refinement)

SupramoleculeName: FCoV-23 S long with Do in mixed conformations (global refinement)
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 / Details: S long with Do in mixed conformations / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Feline coronavirus / Strain: FCoV-23
Molecular weightTheoretical: 162.599625 KDa
Recombinant expressionOrganism: Mammalia (mammals)
SequenceString: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTIKPNNDCR QVNVTQLDGN ENLIRDFLFQ NFKEEGTVVV GGYYPTEVWY NCSKTLTTT AYAYFNNIHA FYFDMEAMEN STGNARGKPL LFHVHGEPVS VIIYISAYGD DVQHRPLLKH GLVCITKTRN V DYNSFTSS ...String:
MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTIKPNNDCR QVNVTQLDGN ENLIRDFLFQ NFKEEGTVVV GGYYPTEVWY NCSKTLTTT AYAYFNNIHA FYFDMEAMEN STGNARGKPL LFHVHGEPVS VIIYISAYGD DVQHRPLLKH GLVCITKTRN V DYNSFTSS QWNSICTGND RKVPFSVIPT DNGTKIYGLE WNDELVTAYI SGRSYNWNIN NNWFNNVTLM YSRSSTATWL HS AAYVYQG VSNFTYYKLN NTNGLKTYEF CEDYEYCTGY ATNVFAPTVG GYIPDGFSFN NWFLLTNDST FVSGRFVTNQ PLL VNCLWP VPSFGVAAQE FCFEGAQFSQ CNGVSLNNTV DVIRFNLNFT ADVQSGMGAT VFSLNTTGGV ILEISCYNDT VRES SFYSY GEIPFGITDG PKYCYVLYNG TALKYLGTLP PSVKEIAISK WGHFYINGYN FFSTFPIDCI SFNLTTSTSG AFWTI AYTS YTEALVQVEN TAIKKVTYCN SHINNIKCSQ LTANLQNGFY PVASSEVGLV NKSVVLLPSF YSHTSVNITI DLGMKL SGY GQPIASALSN ITLPMQDNNT DVYCIRSNQF SVYVHSTCKS SLWDNVFNSD CTDVLHATAV IKTGTCPFSF DKLNNYL TF NKFCLSLHPV GANCKFDVAA RTRTNEQVVR SLYVIYEEGD NIAGVPSDNS GLHDLSVLHL DSCTDYNIYG KTGIGIIR Q TNSTLLSGLY YTSLSGDLLG FKNVTDGVVY SVTPCDVSAQ AAVIDGTIVG AMTSINSELL GLTHWTTTPN FYYYSIYNY TNERTRGTAI DSNDVDCEPI ITYSNIGVCK NGALVFINVT HSDGDVQPIS TGNVTIPTNF TISVQVEYIQ VYTTPVSIDC SRYVCNGNP RCNKLLTQYV SACQTIEQAL AMGARLENME VDSMLFVSEN ALKLASVEAF NSTEHLDPIY KEWPNIGGSW L GGLKDILP SHNSKRKYRS AIEDLLFDKV VTSGLGTVDE DYKRCTGGYD IADLVCAQYY NGIMVLPGVA NDDKMTMYTA SL AGGITLG ALGGGAVAIP FAVAVQARLN YVALQTDVLN KNQQILANAF NQAIGNITQA FGKVNDAIHQ TSKGLATVAK ALA KVQDVV NTQGQALSHL TVQLQNNFQA ISSSISDIYN RLDPPSADAQ VDRLITGRLT ALNAFVSQTL TRQAEVRASR QLAK DKVNE CVRSQSQRFG FCGNGTHLFS LANAAPNGMI FFHTVLLPTA YETVTAWSGI CASDGDHTFG LVVKDVQLTL FRNLD DKFY LTPRTMYQPR VATISDFVQI EGCDVLFVNA TVIELPGIIP DYIDINQTVQ DILENYRPNW TVPELTLDIF NSTYLN LTG EINDLEFRSE KLHNTTVELA VLIDNINNTL VNLEWLNRIE TYVKSGGYIP EAPRDGQAYV RKDGEWVLLS TFLVPRG SG GSGGSGLNDI FEAQKIEWHE GGSHHHHHHH H

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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: 40 / 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: PALMITOLEIC ACID

MacromoleculeName: PALMITOLEIC ACID / type: ligand / ID: 6 / Number of copies: 4 / Formula: PAM
Molecular weightTheoretical: 254.408 Da
Chemical component information

ChemComp-PAM:
PALMITOLEIC ACID

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Macromolecule #7: water

MacromoleculeName: water / type: ligand / ID: 7 / Number of copies: 76 / 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: 1.7 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: PDB ENTRY
PDB model - PDB ID:

7usb

Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 213214
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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