Lipid bilayers regulate allosteric signal of NMDA receptor GluN1 C-terminal domain

NMDAR (N-methyl-D-aspartate receptor) consisted of GluN1 and GluN2, and/or GluN3 subunits. As the obligatory subunit of NMDAR, GluN1 contains variant N-terminal domain (NTD) and C-terminal domain (CTD). The CTD contains allosteric signal and mediates the metabotropic function of NMDAR, which has been confirmed by previous studies. However, the allosteric signaling mechanism of GluN1 CTD has not been studied. In our study, we found that GluN1 CTD could bind to the lipid bilayers and affect the antigen epitope of GluN1 C-terminal antibody, suggesting that membrane binding may determine the allosteric signal of GluN1 CTD. In addition, we discovered that the membrane binding of GluN1 CTD could be regulated by the phosphorylation of GluN1 CTD C1 region. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

NMDAR is composed of GluN1 and GluN2, and/or GluN3 subunits, with GluN1 serving as the obligatory subunit containing variant N-terminal domain (NTD) and C-terminal domain (CTD). Through our study, we found that GluN1 CTD could bind to lipid bilayers and affect its antigen epitope, suggesting that membrane binding may determine the allosteric signal of GluN1 CTD. Additionally, we discovered that the membrane binding of GluN1 CTD can be regulated by the phosphorylation of GluN1 CTD C1 region.