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 journalArticle

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 electrophysiological recording, we show that the synthetic Mag-1 peptides cause noncompetitive inhibition of the receptor channel activity.

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

Fingerprint

Glutamate Receptors
N-Methylaspartate
N-Methyl-D-Aspartate Receptors
Peptides
Ligands
Calcium
Ions
Bacteriophages
Clamping devices
Modulators
Ligand-Gated Ion Channels
Plasticity
Amino acids
Peptide Library
Brain
Cyclic Peptides
Social Identification
Neuronal Plasticity
Fusion reactions
Genes

Keywords

  • neurotoxicity
  • NMDA
  • peptide display

ASJC Scopus subject areas

  • Microbiology

Cite this

Li, M., Yu, W., Chen, C. H., Cwirla, S., Whitehorn, E., Tate, E., ... Dower, B. (1996). In vitro selection of peptides acting at a new site of NMDA glutamate receptors. Nature Biotechnology, 14(8), 986-991.

In vitro selection of peptides acting at a new site of NMDA glutamate receptors. / Li, Min; Yu, Weifeng; Chen, Chien Huan; Cwirla, Steve; Whitehorn, Erik; Tate, Emily; Raab, Ron; Bremer, Meire; Dower, Bill.

In: Nature Biotechnology, Vol. 14, No. 8, 08.1996, p. 986-991.

Research output: Contribution to journalArticle

Li, M, Yu, W, Chen, CH, Cwirla, S, Whitehorn, E, Tate, E, Raab, R, Bremer, M & Dower, B 1996, 'In vitro selection of peptides acting at a new site of NMDA glutamate receptors', Nature Biotechnology, vol. 14, no. 8, pp. 986-991.
Li M, Yu W, Chen CH, Cwirla S, Whitehorn E, Tate E et al. In vitro selection of peptides acting at a new site of NMDA glutamate receptors. Nature Biotechnology. 1996 Aug;14(8):986-991.
Li, Min ; Yu, Weifeng ; Chen, Chien Huan ; Cwirla, Steve ; Whitehorn, Erik ; Tate, Emily ; Raab, Ron ; Bremer, Meire ; Dower, Bill. / In vitro selection of peptides acting at a new site of NMDA glutamate receptors. In: Nature Biotechnology. 1996 ; Vol. 14, No. 8. pp. 986-991.
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