Abstract
The ionotropic glutamate receptor mediate fast neuronal transmission in vertebrate central nerve system. Although several models have been proposed, the subunit stoichiometry and symmetry of ionotropic glutamate receptors (iGluRs) remain unclear. The recent theory that iGluR consists of two dimers in a tetramer formation raised the possibility that the iGluR have twofold symmetric structure, in contrast to fourfold symmetric structure of potassium channels. We have developed a new approach to investigate the conformation of functional channels. The N-terminal extracellular LIVBP domain of GluR1 subtype of iGluR was replaced by leucine zipper peptides designed to form stable symmetric dimers, trimers, tetramers or pentamers. Although the LIVBP domain has been proposed to form initial dimers, channel function was only restored by the tetramer-forming peptide. Furthermore, engineered metal bridge method, which measures the distance between cysteine residues, indicated that the channel domain adopts fourfold symmetric tetramer in functional GluR1 channels. Therefore, we propose that GluR1 assembles as a fourfold symmetric tetramer, and the LIVBP domain plays an important role in achieving this conformation. [Jpn J Physiol 54 Suppl:S139 (2004)]
