Allosteric activation of membrane-bound glutamate receptors using coordination chemistry within living cells

Shigeki Kiyonaka, Ryou Kubota, Yukiko Michibata, Masayoshi Sakakura, Hideo Takahashi, Tomohiro Numata, Ryuji Inoue, Michisuke Yuzaki, Itaru Hamachi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The controlled activation of proteins in living cells is an important goal in protein-design research, but to introduce an artificial activation switch into membrane proteins through rational design is a significant challenge because of the structural and functional complexity of such proteins. Here we report the allosteric activation of two types of membrane-bound neurotransmitter receptors, the ion-channel type and the G-protein-coupled glutamate receptors, using coordination chemistry in living cells. The high programmability of coordination chemistry enabled two His mutations, which act as an artificial allosteric site, to be semirationally incorporated in the vicinity of the ligand-binding pockets. Binding of Pd(2,2′-bipyridine) at the allosteric site enabled the active conformations of the glutamate receptors to be stabilized. Using this approach, we were able to activate selectively a mutant glutamate receptor in live neurons, which initiated a subsequent signal-transduction pathway.

Original languageEnglish
Pages (from-to)958-967
Number of pages10
JournalNature Chemistry
Volume8
Issue number10
DOIs
Publication statusPublished - 2016 Oct 1

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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    Kiyonaka, S., Kubota, R., Michibata, Y., Sakakura, M., Takahashi, H., Numata, T., Inoue, R., Yuzaki, M., & Hamachi, I. (2016). Allosteric activation of membrane-bound glutamate receptors using coordination chemistry within living cells. Nature Chemistry, 8(10), 958-967. https://doi.org/10.1038/nchem.2554