5OJK

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

Summary for 5OJK

• Entry DOI: 10.2210/pdb5ojk/pdb
• Descriptor: Neuroligin-1,Neuroligin-1, 2-acetamido-2-deoxy-beta-D-glucopyranose, TRIETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: neuroligin-neurexin, synaptic organizer protein, spliced sequence b, cell adhesion
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 132162.05

Authors

Elegheert, J.,Aricescu, A.R. (deposition date: 2017-07-21, release date: 2017-08-23, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.55 Å)