Organelle or cellular component: Contactin 2 Ig1-Ig6
Protein or peptide: Contactin-2
Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Keywords
contactins / adhesion molecule / protein structure / conformational changes / homodimer / MEMBRANE PROTEIN
Function / homology
Function and homology information
establishment of protein localization to juxtaparanode region of axon / presynaptic membrane organization / reduction of food intake in response to dietary excess / L1CAM interactions / clustering of voltage-gated potassium channels / dendrite self-avoidance / protein localization to juxtaparanode region of axon / cell-cell adhesion mediator activity / NrCAM interactions / axon initial segment ...establishment of protein localization to juxtaparanode region of axon / presynaptic membrane organization / reduction of food intake in response to dietary excess / L1CAM interactions / clustering of voltage-gated potassium channels / dendrite self-avoidance / protein localization to juxtaparanode region of axon / cell-cell adhesion mediator activity / NrCAM interactions / axon initial segment / node of Ranvier / juxtaparanode region of axon / NCAM1 interactions / fat cell differentiation / homophilic cell adhesion via plasma membrane adhesion molecules / side of membrane / axon guidance / synapse organization / myelin sheath / postsynaptic membrane / cell adhesion / axon / synapse / plasma membrane Similarity search - Function
: / Immunoglobulin domain / Immunoglobulin I-set / Immunoglobulin I-set domain / Fibronectin type III domain / Fibronectin type 3 domain / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Fibronectin type-III domain profile. / Fibronectin type III ...: / Immunoglobulin domain / Immunoglobulin I-set / Immunoglobulin I-set domain / Fibronectin type III domain / Fibronectin type 3 domain / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold Similarity search - Domain/homology
National Institutes of Health/National Institute of Mental Health (NIH/NIMH)
United States
Citation
Journal: Structure / Year: 2024 Title: Molecular mechanism of contactin 2 homophilic interaction. Authors: Shanghua Fan / Jianfang Liu / Nicolas Chofflet / Aaron O Bailey / William K Russell / Ziqi Zhang / Hideto Takahashi / Gang Ren / Gabby Rudenko / Abstract: Contactin 2 (CNTN2) is a cell adhesion molecule involved in axon guidance, neuronal migration, and fasciculation. The ectodomains of CNTN1-CNTN6 are composed of six Ig domains (Ig1-Ig6) and four FN ...Contactin 2 (CNTN2) is a cell adhesion molecule involved in axon guidance, neuronal migration, and fasciculation. The ectodomains of CNTN1-CNTN6 are composed of six Ig domains (Ig1-Ig6) and four FN domains. Here, we show that CNTN2 forms transient homophilic interactions (K ∼200 nM). Cryo-EM structures of full-length CNTN2 and CNTN2_Ig1-Ig6 reveal a T-shaped homodimer formed by intertwined, parallel monomers. Unexpectedly, the horseshoe-shaped Ig1-Ig4 headpieces extend their Ig2-Ig3 tips outwards on either side of the homodimer, while Ig4, Ig5, Ig6, and the FN domains form a central stalk. Cross-linking mass spectrometry and cell-based binding assays confirm the 3D assembly of the CNTN2 homodimer. The interface mediating homodimer formation differs between CNTNs, as do the homophilic versus heterophilic interaction mechanisms. The CNTN family thus encodes a versatile molecular platform that supports a very diverse portfolio of protein interactions and that can be leveraged to strategically guide neural circuit development.
Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 281 K / Instrument: LEICA EM GP
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Electron microscopy
Microscope
TFS KRIOS
Specialist optics
Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV
Image recording
Film or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 1 / Number real images: 4297 / Average exposure time: 7.39 sec. / Average electron dose: 50.0 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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