Journal
CURRENT OPINION IN STRUCTURAL BIOLOGY
Volume 54, Issue -, Pages 34-42Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.sbi.2018.12.009
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Funding
- National Institutes of Health [MH085926, GM105730]
- Robertson Funds at Cold Spring Harbor Laboratory
- Stanley Institute of Cognitive Genomics
- Boehringer Ingelheim Fonds
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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.
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