6PNP

Crystal structure of the splice insert-free neurexin-1 LNS2 domain in complex with neurexophilin-1

6PNP の概要

• エントリーDOI: 10.2210/pdb6pnp/pdb
• 分子名称: Neurexin-1, Neurexophilin-1 (3 entities in total)
• 機能のキーワード: synapse, complex, splice-variant, cell adhesion
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40215.18

構造登録者

Wilson, S.C.,White, K.I.,Zhou, Q.,Brunger, A.T. (登録日: 2019-07-02, 公開日: 2019-10-09, 最終更新日: 2024-10-23)

主引用文献

Wilson, S.C.,White, K.I.,Zhou, Q.,Pfuetzner, R.A.,Choi, U.B.,Sudhof, T.C.,Brunger, A.T.
Structures of neurexophilin-neurexin complexes reveal a regulatory mechanism of alternative splicing.
Embo J., 38:e101603-e101603, 2019

PubMed Abstract: Neurexins are presynaptic, cell-adhesion molecules that specify the functional properties of synapses via interactions with trans-synaptic ligands. Neurexins are extensively alternatively spliced at six canonical sites that regulate multifarious ligand interactions, but the structural mechanisms underlying alternative splicing-dependent neurexin regulation are largely unknown. Here, we determined high-resolution structures of the complex of neurexophilin-1 and the second laminin/neurexin/sex-hormone-binding globulin domain (LNS2) of neurexin-1 and examined how alternative splicing at splice site #2 (SS2) regulates the complex. Our data reveal a unique, extensive, neurexophilin-neurexin binding interface that extends the jelly-roll β-sandwich of LNS2 of neurexin-1 into neurexophilin-1. The SS2A insert of LNS2 augments this interface, increasing the binding affinity of LNS2 for neurexophilin-1. Taken together, our data reveal an unexpected architecture of neurexophilin-neurexin complexes that accounts for the modulation of binding by alternative splicing, which in turn regulates the competition of neurexophilin for neurexin binding with other ligands.

PubMed: 31566781
DOI: 10.15252/embj.2019101603

実験手法

X-RAY DIFFRACTION (1.94 Å)