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Structural Insights into Modulation of Neurexin-Neuroligin Trans-synaptic Adhesion by MDGA1/Neuroligin-2 Complex

Title
Structural Insights into Modulation of Neurexin-Neuroligin Trans-synaptic Adhesion by MDGA1/Neuroligin-2 Complex
Authors
Kim, Jung A.Kim, DoyounWon, Seoung YounHan, Kyung AhPark, DongseokCho, EunjuYun, NayoungAn, Hyun JooUm, Ji WonKim, EunjoonLee, Jie-OhKo, JaewonKim, Ho Min
DGIST Authors
Han, Kyung Ah; Park, Dongseok; Cho, Eunju; Um, Ji WonKo, Jaewon
Issue Date
2017-06
Citation
Neuron, 94(6), 1121-1131
Type
Article
Article Type
Article
Keywords
Cell AdhesionCrystal StructureDiseaseInhibitory Synapse DevelopmentMDGASMoleculesProtein
ISSN
0896-6273
Abstract
Membrane-associated mucin domain-containing glycosylphosphatidylinositol anchor proteins (MDGAs) bind directly to neuroligin-1 (NL1) and neuroligin-2 (NL2), thereby respectively regulating excitatory and inhibitory synapse development. However, the mechanisms by which MDGAs modulate NL activity to specify development of the two synapse types remain unclear. Here, we determined the crystal structures of human NL2/MDGA1 Ig1-3 complex, revealing their stable 2: 2 arrangement with three interaction interfaces. Cell-based assays using structure-guided, site-directed MDGA1 mutants showed that all three contact patches were required for the MDGA's negative regulation of NL2-mediated synaptogenic activity. Furthermore, MDGA1 competed with neurexins for NL2 via its Ig1 domain. The binding affinities of both MDGA1 and MDGA2 for NL1 and NL2 were similar, consistent with the structural prediction of similar binding interfaces. However, MDGA1 selectively associated with NL2, but not NL1, in vivo. These findings collectively provide structural insights into the mechanism by which MDGAs negatively modulate synapse development governed by NLs/neurexins.
URI
http://hdl.handle.net/20.500.11750/4147
DOI
10.1016/j.neuron.2017.05.034
Publisher
CELL PRESS
Related Researcher
  • Author Ko, Jae Won Laboratory of Synapse Formation and Function
  • Research Interests Neuroendocine Regulation by Gut-Microbiota derived Small Chain fatty Acids (SCFA); Neural Immune Regulation by Medium/Small Chain Fatty Acids (MCFA); Odorant G-protein Coupled Receptors (GPCRs) Structure and Function; Ectopic Odorant GPCRs and Endocrine Diseases
Files:
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Collection:
Brain and Cognitive SciencesUm Laboratory1. Journal Articles
ETC1. Journal Articles


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