5V5W
Molecular Mechanism of MDGA1: Regulation of Neuroligin 2:Neurexin Trans-synaptic Bridges
Summary for 5V5W
| Entry DOI | 10.2210/pdb5v5w/pdb |
| Related | 5V5V |
| Descriptor | MAM domain-containing glycosylphosphatidylinositol anchor protein 1, SULFATE ION (3 entities in total) |
| Functional Keywords | synaptic organizer, regulatory molecule, mdgas, cell adhesion |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 26219.34 |
| Authors | Machius, M.,Gangwar, S.P.,Rudenko, G. (deposition date: 2017-03-15, release date: 2017-07-05, Last modification date: 2024-11-20) |
| Primary citation | Gangwar, S.P.,Zhong, X.,Seshadrinathan, S.,Chen, H.,Machius, M.,Rudenko, G. Molecular Mechanism of MDGA1: Regulation of Neuroligin 2:Neurexin Trans-synaptic Bridges. Neuron, 94:1132-1141.e4, 2017 Cited by PubMed Abstract: Neuroligins and neurexins promote synapse development and validation by forming trans-synaptic bridges spanning the synaptic cleft. Select pairs promote excitatory and inhibitory synapses, with neuroligin 2 (NLGN2) limited to inhibitory synapses and neuroligin 1 (NLGN1) dominating at excitatory synapses. The cell-surface molecules, MAM domain-containing glycosylphosphatidylinositol anchor 1 (MDGA1) and 2 (MDGA2), regulate trans-synaptic adhesion between neurexins and neuroligins, impacting NLGN2 and NLGN1, respectively. We have determined the molecular mechanism of MDGA action. MDGA1 Ig1-Ig2 is sufficient to bind NLGN2 with nanomolar affinity; its crystal structure reveals an unusual locked rod-shaped array. In the crystal structure of the complex, two MDGA1 Ig1-Ig2 molecules each span the entire NLGN2 dimer. Site-directed mutagenesis confirms the observed interaction interface. Strikingly, Ig1 from MDGA1 binds to the same region on NLGN2 as neurexins do. Thus, MDGAs regulate the formation of neuroligin-neurexin trans-synaptic bridges by sterically blocking access of neurexins to neuroligins. PubMed: 28641112DOI: 10.1016/j.neuron.2017.06.009 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.718 Å) |
Structure validation
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