5oj6
From Proteopedia
Crystal structure of the chicken MDGA1 ectodomain in complex with the human neuroligin 1 (NL1(-A-B)) cholinesterase domain.
Structural highlights
FunctionNLGN1_HUMAN Cell surface protein involved in cell-cell-interactions via its interactions with neurexin family members. Plays a role in synapse function and synaptic signal transmission, and probably mediates its effects by recruiting and clustering other synaptic proteins. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. May be involved in specification of excitatory synapses. Required to maintain wakefulness quality and normal synchrony of cerebral cortex activity during wakefulness and sleep.[UniProtKB:Q99K10] Publication Abstract from PubMedNeuroligin-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. Structural Mechanism for Modulation of Synaptic Neuroligin-Neurexin Signaling by MDGA Proteins.,Elegheert J, Cvetkovska V, Clayton AJ, Heroven C, Vennekens KM, Smukowski SN, Regan MC, Jia W, Smith AC, Furukawa H, Savas JN, de Wit J, Begbie J, Craig AM, Aricescu AR Neuron. 2017 Aug 16;95(4):896-913.e10. doi: 10.1016/j.neuron.2017.07.040. PMID:28817804[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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