Subunit arrangement in P2X receptors

Lin Hua Jiang, Miran Kim, Valeria Spelta, Xuenong Bo, Annmarie Surprenant, R. Ala North

Research output: Contribution to journalArticlepeer-review

Abstract

ATP-gated ionotropic receptors (P2X receptors) are distributed widely in the nervous system. For example, a hetero-oligomeric receptor containing both P2X2 and P2X3 subunits is involved in primary afferent sensation. Each subunit has two membrane-spanning domains. We have used disulfide bond formation between engineered cysteines to demonstrate close proximity between the outer ends of the first transmembrane domain of one subunit and the second transmembrane domain of another. After expression in HEK 293 cells of such modified P2X2 or P2X4 subunits, the disulfide bond formation is evident because an ATP-evoked channel opening requires previous reduction with dithiothreitol. In the hetero-oligomeric P2X2/3 receptor the coexpression of doubly substituted subunits with wild-type partners allows us to deduce that the hetero-oligomeric channel contains adjacent P2X3 subunits but does not contain adjacent P2X2 subunits. The results suggest a "head-to-tail" subunit arrangement in the quaternary structure of P2X receptors and show that a trimeric P2X2/3 receptor would have the composition P2X 2(P2X3)2.
Original languageEnglish
Pages (from-to)8903-8910
Number of pages7
JournalJournal of Neuroscience
Volume23
Issue number26
Publication statusPublished - 1 Oct 2003

Keywords

  • ATP-gated channels
  • Disulfide bonds
  • Ligand-gated channel
  • P2X receptors
  • Subunit order
  • Subunit stoichiometry

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