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- PDB-9gh5: Complex of Fusobacterium nucleatum CbpF with human CEACAM1 -

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Basic information

Entry
Database: PDB / ID: 9gh5
TitleComplex of Fusobacterium nucleatum CbpF with human CEACAM1
Components
  • Carcinoembryonic antigen-related cell adhesion molecule 1
  • Cell surface protein
KeywordsCELL ADHESION / bacterial pathogenesis / adhesin / immunomodulation / host-pathogen interaction
Function / homology
Function and homology information


regulation of endothelial cell differentiation / insulin receptor internalization / negative regulation of cytotoxic T cell degranulation / Regulation of MITF-M dependent genes involved in invasion / granulocyte colony-stimulating factor signaling pathway / regulation of homophilic cell adhesion / negative regulation of hepatocyte proliferation / regulation of epidermal growth factor receptor signaling pathway / filamin binding / regulation of blood vessel remodeling ...regulation of endothelial cell differentiation / insulin receptor internalization / negative regulation of cytotoxic T cell degranulation / Regulation of MITF-M dependent genes involved in invasion / granulocyte colony-stimulating factor signaling pathway / regulation of homophilic cell adhesion / negative regulation of hepatocyte proliferation / regulation of epidermal growth factor receptor signaling pathway / filamin binding / regulation of blood vessel remodeling / regulation of sprouting angiogenesis / negative regulation of lipid biosynthetic process / negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target / negative regulation of T cell mediated cytotoxicity / regulation of endothelial cell migration / negative regulation of granulocyte differentiation / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / insulin catabolic process / Fibronectin matrix formation / common myeloid progenitor cell proliferation / cell-cell adhesion via plasma-membrane adhesion molecules / negative regulation of interleukin-1 production / negative regulation of fatty acid biosynthetic process / positive regulation of vasculogenesis / negative regulation of platelet aggregation / bile acid transmembrane transporter activity / negative regulation of vascular permeability / regulation of immune system process / wound healing, spreading of cells / negative regulation of T cell receptor signaling pathway / transport vesicle membrane / bile acid and bile salt transport / microvillus membrane / blood vessel development / homophilic cell adhesion via plasma membrane adhesion molecules / tertiary granule membrane / lateral plasma membrane / regulation of ERK1 and ERK2 cascade / specific granule membrane / negative regulation of protein kinase activity / basal plasma membrane / protein tyrosine kinase binding / regulation of cell migration / integrin-mediated signaling pathway / Cell surface interactions at the vascular wall / adherens junction / cell outer membrane / regulation of cell growth / kinase binding / cellular response to insulin stimulus / cell junction / cell migration / cell-cell junction / protein transport / actin binding / angiogenesis / protein phosphatase binding / calmodulin binding / protein dimerization activity / cell adhesion / apical plasma membrane / Neutrophil degranulation / cell surface / signal transduction / protein homodimerization activity / extracellular exosome / identical protein binding / membrane / plasma membrane
Similarity search - Function
Trimeric autotransporter adhesin YadA-like, head domain / YadA head domain repeat (2 copies) / : / Trimeric autotransporter adhesin YadA-like, stalk domain / Coiled stalk of trimeric autotransporter adhesin / Trimeric autotransporter adhesin YadA-like, C-terminal membrane anchor domain / YadA-like membrane anchor domain / Pilin-like / Serralysin-like metalloprotease, C-terminal / Immunoglobulin domain ...Trimeric autotransporter adhesin YadA-like, head domain / YadA head domain repeat (2 copies) / : / Trimeric autotransporter adhesin YadA-like, stalk domain / Coiled stalk of trimeric autotransporter adhesin / Trimeric autotransporter adhesin YadA-like, C-terminal membrane anchor domain / YadA-like membrane anchor domain / Pilin-like / Serralysin-like metalloprotease, C-terminal / Immunoglobulin domain / Immunoglobulin / Immunoglobulin domain / Immunoglobulin domain / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Cell adhesion molecule CEACAM1 / Cell surface protein
Similarity search - Component
Biological speciesFusobacterium nucleatum (bacteria)
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å
AuthorsMarongiu, G.L. / Fink, U. / Roderer, D.
Funding support Germany, 1items
OrganizationGrant numberCountry
Leibniz Association Germany
CitationJournal: Proc Natl Acad Sci U S A / Year: 2025
Title: Structural basis for immune cell binding of via the trimeric autotransporter adhesin CbpF.
Authors: Gian Luca Marongiu / Uwe Fink / Felix Schöpf / Andreas Oder / Jens Peter von Kries / Daniel Roderer /
Abstract: (Fn), a commensal in the human oral cavity, is overrepresented in the colon microbiota of colorectal cancer (CRC) patients and is linked to tumor chemoresistance, metastasis, and a poor therapeutic ... (Fn), a commensal in the human oral cavity, is overrepresented in the colon microbiota of colorectal cancer (CRC) patients and is linked to tumor chemoresistance, metastasis, and a poor therapeutic prognosis. Fn produces numerous adhesins that mediate tumor colonization and downregulation of the host's antitumor immune response. One of these, the trimeric autotransporter adhesin (TAA) CEACAM binding protein of (CbpF), targets CEACAM1 on T-cells and has been associated with immune evasion of Fn-colonized tumors. Whereas the role of CEACAM1 in homophilic and heterophilic cell interactions and immune evasion is well described, the mechanistic details of its interaction with fusobacterial CbpF remain unknown due to the lack of a high-resolution structure of the adhesin-receptor complex. Here, we present two structures of CbpF alone and in complex with CEACAM1, obtained by cryogenic electron microscopy and single particle analysis. They reveal that CbpF forms a stable homotrimeric complex whose N-terminal part of the extracellular domain comprises a 64 Å long β roll domain with a unique lateral loop extension. CEACAM1 binds to this loop with high affinity via its N-terminal IgV-like domain with a nanomolar dissociation constant as determined by surface plasmon resonance. This study provides a comprehensive structural description of a fusobacterial TAA, illustrates a yet undescribed CEACAM1 binding mode, and paves the way for rational drug design targeting Fn in CRC.
History
DepositionAug 15, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 2, 2025Provider: repository / Type: Initial release
Revision 1.0Apr 2, 2025Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Apr 2, 2025Data content type: Additional map / Part number: 1 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0Apr 2, 2025Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
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Revision 1.1Apr 16, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
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Revision 1.2Apr 23, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Cell surface protein
B: Cell surface protein
C: Cell surface protein
D: Carcinoembryonic antigen-related cell adhesion molecule 1
E: Carcinoembryonic antigen-related cell adhesion molecule 1
F: Carcinoembryonic antigen-related cell adhesion molecule 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)291,92424
Polymers287,9426
Non-polymers3,98218
Water543
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Protein Cell surface protein


Mass: 51827.051 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Details: full length protein, residues 25-274 are resolved / Source: (gene. exp.) Fusobacterium nucleatum (bacteria) / Gene: FN1499 / Production host: Escherichia coli (E. coli) / References: UniProt: Q8RIS0
#2: Protein Carcinoembryonic antigen-related cell adhesion molecule 1 / Biliary glycoprotein 1 / BGP-1


Mass: 44153.664 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Details: CEACAM1 extracellular domain with C-terminal histag (Acro Biosystems)
Source: (gene. exp.) Homo sapiens (human) / Gene: CEACAM1, BGP, BGP1 / Production host: Homo sapiens (human) / References: UniProt: P13688
#3: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 18 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Hetero-hexameric complex of CbpF homotrimer with 3 CEACAM1 bound
Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT
Molecular weightValue: 0.35 MDa / Experimental value: NO
Source (natural)Organism: Fusobacterium nucleatum (bacteria)
Source (recombinant)Organism: Escherichia coli (E. coli)
Buffer solutionpH: 7
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal magnification: 105000 X / Nominal defocus max: 2400 nm / Nominal defocus min: 1200 nm / Alignment procedure: ZEMLIN TABLEAU
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 52.8 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 6334
EM imaging opticsEnergyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV

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Processing

EM software
IDNameVersionCategory
1cryoSPARC4.4.0particle selection
2EPU2.12image acquisition
4cryoSPARC4.4.0CTF correction
7Cootmodel fitting
9cryoSPARC4.4.0initial Euler assignment
10cryoSPARC4.4.0final Euler assignment
11cryoSPARC4.4.0classification
12cryoSPARC4.4.03D reconstruction
13PHENIX1.21-5207model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 1766853
SymmetryPoint symmetry: C3 (3 fold cyclic)
3D reconstructionResolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 211927 / Num. of class averages: 1 / Symmetry type: POINT
Atomic model buildingProtocol: FLEXIBLE FIT / Space: REAL
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00310569
ELECTRON MICROSCOPYf_angle_d0.68414358
ELECTRON MICROSCOPYf_dihedral_angle_d10.4011565
ELECTRON MICROSCOPYf_chiral_restr0.0531635
ELECTRON MICROSCOPYf_plane_restr0.0061908

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