5OJK

Crystal structure of the human neuroligin 1 cholinesterase domain containing spliced sequence B (SSB) (NL1(-A+B))

5OJK の概要

• エントリーDOI: 10.2210/pdb5ojk/pdb
• 分子名称: Neuroligin-1,Neuroligin-1, 2-acetamido-2-deoxy-beta-D-glucopyranose, TRIETHYLENE GLYCOL, ... (4 entities in total)
• 機能のキーワード: neuroligin-neurexin, synaptic organizer protein, spliced sequence b, cell adhesion
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 132162.05

構造登録者

Elegheert, J.,Aricescu, A.R. (登録日: 2017-07-21, 公開日: 2017-08-23, 最終更新日: 2024-10-23)

主引用文献

Elegheert, J.,Cvetkovska, V.,Clayton, A.J.,Heroven, C.,Vennekens, K.M.,Smukowski, S.N.,Regan, M.C.,Jia, W.,Smith, A.C.,Furukawa, H.,Savas, J.N.,de Wit, J.,Begbie, J.,Craig, A.M.,Aricescu, A.R.
Structural Mechanism for Modulation of Synaptic Neuroligin-Neurexin Signaling by MDGA Proteins.
Neuron, 95:896-913.e10, 2017

PubMed Abstract: Neuroligin-neurexin (NL-NRX) complexes are fundamental synaptic organizers in the central nervous system. An accurate spatial and temporal control of NL-NRX signaling is crucial to balance excitatory and inhibitory neurotransmission, and perturbations are linked with neurodevelopmental and psychiatric disorders. MDGA proteins bind NLs and control their function and interaction with NRXs via unknown mechanisms. Here, we report crystal structures of MDGA1, the NL1-MDGA1 complex, and a spliced NL1 isoform. Two large, multi-domain MDGA molecules fold into rigid triangular structures, cradling a dimeric NL to prevent NRX binding. Structural analyses guided the discovery of a broad, splicing-modulated interaction network between MDGA and NL family members and helped rationalize the impact of autism-linked mutations. We demonstrate that expression levels largely determine whether MDGAs act selectively or suppress the synapse organizing function of multiple NLs. These results illustrate a potentially brain-wide regulatory mechanism for NL-NRX signaling modulation.

PubMed: 28817804
DOI: 10.1016/j.neuron.2017.07.040

実験手法

X-RAY DIFFRACTION (2.55 Å)