Dissecting diverse functions of NMDA receptors by structural biology

Curr Opin Struct Biol. 2019 Feb;54:34-42. doi: 10.1016/j.sbi.2018.12.009. Epub 2019 Jan 28.

Abstract

N-Methyl-d-aspartate receptors (NMDARs) are glutamate-gated ion channels, which are critically involved in brain development, learning and memory, cognition, as well as a number of neurological diseases and disorders. Structural biology of NMDARs has been challenging due to technical difficulties associated with assembling a number of different membrane protein subunits. Here, we review historical X-ray crystallographic studies on isolated extracellular domains, which are still the most effective mean to delineate compound binding modes, as well as the most recent studies using electron cryo-microscopy (cryo-EM). A number of NMDAR structures accumulated over the past 15 years provide insights into the hetero-tetrameric assembly pattern, pharmacological specificities elicited by subtypes and alternative splicing, and potential patterns of conformational dynamics; however, many more important unanswered questions remain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Extracellular Space / metabolism
  • Humans
  • Protein Domains
  • Receptors, N-Methyl-D-Aspartate / chemistry*
  • Receptors, N-Methyl-D-Aspartate / metabolism*

Substances

  • Receptors, N-Methyl-D-Aspartate