Molecular dissection of the agonist binding site of an AMPA receptor

Arja Kuusinen, Milla Arvola, Kari Keinänen (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

172 Citations (Scopus)

Abstract

Two discontinuous segments (S1 and S2), separated by membrane-associated domains, in ionotropic glutamate receptor (GluR) subunits show sequence similarity to bacterial periplasmic amino acid-binding proteins, suggesting an evolutionary and structural relationship.
Experimental evidence arguing for and against the inferred extracellular location of the S1 and S2 domains in GluRs has been presented. Here, we report that an extracellularly expressed fusion protein consisting of the S1 and S2 domains of alpha-amino-5-methyl-3-hydroxyisoxazolone-4-propionate (AMPA)-selective glutamate receptor GluR-D joined together via a hydrophilic linker peptide specifically reproduces the AMPA-binding properties of GluR-D, whereas the separately expressed segments do not bind ligand.
This provides direct evidence that the S1 and S2 segments of GluR-D contain the structural determinants necessary and sufficient for selective agonist binding. Dissection of a functional neurotransmitter binding site as a soluble protein separate from the integral membrane channel will facilitate new approaches to analyse the structure of GluRs.
Original languageEnglish
Pages (from-to)6327-6332
JournalEMBO Journal
Volume14
Issue number24
Publication statusPublished - 1995
MoE publication typeA1 Journal article-refereed

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