In vitro selection of peptides acting at a new site of Nmda glutamate receptors

Min Li, Weifeng Yu, Chien Huan Chen, Steve Cwirla, Erik Whitehorn, Emily Tate, Ron Raab, Meire Bremer, Bill Dower

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Oligomeric N-methyl D-aspartate receptor (NMDAR) in brain is a ligand-gated ion channel that becomes selectively permeable to ions upon binding to ligands. For NMDAR channel, the binding of glutamate and glycine results in opening of the calcium permeable channel. Because the calcium influx mediated by NMDAR is important for synaptic plasticity and excitotoxicity, the function of NMDA receptors has been implicated in both health and disease. Native NMDA receptors are thought to be heteromeric pentamers with a central ion conduction pathway. There are five genes (NR1, 2A, 2B, 2C, and 2D) encoding various subunits that have been cloned, and NR1 is thought to be the essential subunit since it forms a functional channel by itself. To study NMDAR structure and function, we have searched for peptide modulators of NR1 using random peptide bacteriophage libraries. The peptides were identified based on their specific association with a purified receptor fusion protein that contains the putative ligand binding domain. We report the identification of one group of cyclic peptides (Mag-1) with a consensus sequence of CDGLRHMWFC. Using biochemical binding analysis and patch clamp electro-physiological recording, we show that the synthetic Mag-1 peptides cause noncompetitive inhibition of the receptor channel activity.

Original languageEnglish
Pages (from-to)986-991
Number of pages6
JournalNature Biotechnology
Volume14
Issue number8
DOIs
StatePublished - Aug 1996
Externally publishedYes

Fingerprint Dive into the research topics of 'In vitro selection of peptides acting at a new site of Nmda glutamate receptors'. Together they form a unique fingerprint.

Cite this