A steroid modulatory domain on NR2B controls N-methyl-D-aspartate receptor proton sensitivity.

ABSTRACT: N-methyl-D-aspartate (NMDA) receptor function is modulated by several endogenous molecules, including zinc, polyamines, protons, and sulfated neurosteroids. Zinc, polyamines, and phenylethanolamines exert their respective modulatory effects by exacerbating or relieving tonic proton inhibition. Here, we report that pregnenolone sulfate (PS) uses a unique mechanism for enhancement of NMDA receptor function that is independent of the proton sensor. We identify a steroid modulatory domain, SMD1, on the NMDA receptor NR2B subunit that is critical for both PS enhancement and proton sensitivity. This domain includes the J/K helices in the S2 region of the glutamate recognition site and the fourth membrane transmembrane region (M4). A molecular model based on alpha-amino-3-hydroxy-5-methyl-4-isoxa

SUBMITTER: Jang MK 

PROVIDER: S-EPMC419580 | biostudies-literature | 2004 May

REPOSITORIES: biostudies-literature