9BA4

Full-length cross-linked Contactin 2 (CNTN2)

9BA4 の概要

• エントリーDOI: 10.2210/pdb9ba4/pdb
• EMDBエントリー: 44395
• 分子名称: Contactin-2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: contactins, adhesion molecule, protein structure, conformational changes, homodimer, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 220825.80

構造登録者

Liu, J.L.,Fan, S.F.,Ren, G.R.,Rudenko, G.R. (登録日: 2024-04-03, 公開日: 2024-07-17, 最終更新日: 2024-11-20)

主引用文献

Fan, S.,Liu, J.,Chofflet, N.,Bailey, A.O.,Russell, W.K.,Zhang, Z.,Takahashi, H.,Ren, G.,Rudenko, G.
Molecular mechanism of contactin 2 homophilic interaction.
Structure, 32:1652-1666.e8, 2024

PubMed 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 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.

PubMed: 38968938
DOI: 10.1016/j.str.2024.06.004

実験手法

ELECTRON MICROSCOPY (3.54 Å)