5V5V

Complex of NLGN2 with MDGA1 Ig1-Ig2

Summary for 5V5V

• Entry DOI: 10.2210/pdb5v5v/pdb
• Related: 5V5W
• Descriptor: Neuroligin-2, MAM domain-containing glycosylphosphatidylinositol anchor protein 1 (2 entities in total)
• Functional Keywords: synaptic organizers, regulatory complex, neuroligins, mdgas, cell adhesion
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 12
• Total formula weight: 544655.18

Authors

Gangwar, S.P.,Machius, M.,Rudenko, G. (deposition date: 2017-03-15, release date: 2017-07-05, Last modification date: 2024-11-06)

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

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: 28641112
DOI: 10.1016/j.neuron.2017.06.009

Experimental method

X-RAY DIFFRACTION (4.11 Å)