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-Structure paper
タイトル | Molecular mechanism of contactin 2 homophilic interaction. |
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ジャーナル・号・ページ | Structure, Vol. 32, Issue 10, Page 1652-11666.e8, Year 2024 |
掲載日 | 2024年10月3日 |
著者 | Shanghua Fan / Jianfang Liu / Nicolas Chofflet / Aaron O Bailey / William K Russell / Ziqi Zhang / Hideto Takahashi / Gang Ren / Gabby Rudenko / |
PubMed 要旨 | 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. |
リンク | Structure / PubMed:38968938 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.51 - 3.77 Å |
構造データ | EMDB-44395, PDB-9ba4: EMDB-44396, PDB-9ba5: EMDB-44397: Full-length cross-linked Contactin 2 (FN1 apart) |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | MEMBRANE PROTEIN / contactins / adhesion molecule / protein structure / conformational changes / homodimer |