5xeq

Crystal Structure of human MDGA1 and human neuroligin-2 complex

spinqualitylabelsall models 5xeq, resolution 3.14Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5xeq is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.136Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MDGA1_HUMAN Required for radial migration of cortical neurons in the superficial layer of the neocortex (By similarity). Plays a role in the formation or maintenance of inhibitory synapses. May function by inhibiting the activity of NLGN2. Publication Abstract from PubMed 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. Structural Insights into Modulation of Neurexin-Neuroligin Trans-synaptic Adhesion by MDGA1/Neuroligin-2 Complex.,Kim JA, Kim D, Won SY, Han KA, Park D, Cho E, Yun N, An HJ, Um JW, Kim E, Lee JO, Ko J, Kim HM Neuron. 2017 Jun 21;94(6):1121-1131.e6. doi: 10.1016/j.neuron.2017.05.034. PMID:28641111 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Neuroligin

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