Mechanical coupling maintains the fidelity of NMDA receptor-mediated currents.

ABSTRACT: The fidelity of integration of pre- and postsynaptic activity by NMDA receptors (NMDARs) requires a match between agonist binding and ion channel opening. To address how agonist binding is transduced into pore opening in NMDARs, we manipulated the coupling between the ligand-binding domain (LBD) and the ion channel by inserting residues in a linker between them. We found that a single residue insertion markedly attenuated the ability of NMDARs to convert a glutamate transient into a functional response. This was largely a result of a decreased likelihood of the channel opening and remaining open. Computational and thermodynamic analyses suggest that insertions prevent the agonist-bound LBD from effectively pulling on pore lining elements, thereby destabilizing pore opening. Furthermore, th

SUBMITTER: Kazi R 

PROVIDER: S-EPMC4072853 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature