7CEG

Crystal structure of the complex between mouse PTP delta and neuroligin-3

7CEG の概要

• エントリーDOI: 10.2210/pdb7ceg/pdb
• 分子名称: Isoform C of Receptor-type tyrosine-protein phosphatase delta, Neuroligin-3, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: synapse organization, trans-synaptic complex, esterase domain, hydrolase-cell adhesion complex, hydrolase/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: 107777.83

構造登録者

Yamagata, A.,Yoshida, T.,Shiroshima, T.,Maeda, A.,Fukai, S. (登録日: 2020-06-23, 公開日: 2021-02-24, 最終更新日: 2024-11-20)

主引用文献

Yoshida, T.,Yamagata, A.,Imai, A.,Kim, J.,Izumi, H.,Nakashima, S.,Shiroshima, T.,Maeda, A.,Iwasawa-Okamoto, S.,Azechi, K.,Osaka, F.,Saitoh, T.,Maenaka, K.,Shimada, T.,Fukata, Y.,Fukata, M.,Matsumoto, J.,Nishijo, H.,Takao, K.,Tanaka, S.,Okabe, S.,Tabuchi, K.,Uemura, T.,Mishina, M.,Mori, H.,Fukai, S.
Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice.
Nat Commun, 12:1848-1848, 2021

PubMed Abstract: Neuroligin 3 (NLGN3) and neurexins (NRXNs) constitute a canonical transsynaptic cell-adhesion pair, which has been implicated in autism. In autism spectrum disorder (ASD) development of sociality can be impaired. However, the molecular mechanism underlying NLGN3-mediated social development is unclear. Here, we identify non-canonical interactions between NLGN3 and protein tyrosine phosphatase δ (PTPδ) splice variants, competing with NRXN binding. NLGN3-PTPδ complex structure revealed a splicing-dependent interaction mode and competition mechanism between PTPδ and NRXNs. Mice carrying a NLGN3 mutation that selectively impairs NLGN3-NRXN interaction show increased sociability, whereas mice where the NLGN3-PTPδ interaction is impaired exhibit impaired social behavior and enhanced motor learning, with imbalance in excitatory/inhibitory synaptic protein expressions, as reported in the Nlgn3 R451C autism model. At neuronal level, the autism-related Nlgn3 R451C mutation causes selective impairment in the non-canonical pathway. Our findings suggest that canonical and non-canonical NLGN3 pathways compete and regulate the development of sociality.

PubMed: 33758193
DOI: 10.1038/s41467-021-22059-6

実験手法

X-RAY DIFFRACTION (3.85 Å)