RT Journal Article
SR Electronic
T1 Subunit Arrangement in P2X Receptors
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8903
OP 8910
DO 10.1523/JNEUROSCI.23-26-08903.2003
VO 23
IS 26
A1 Lin-Hua Jiang
A1 Miran Kim
A1 Valeria Spelta
A1 Xuenong Bo
A1 Annmarie Surprenant
A1 R. Alan North
YR 2003
UL http://www.jneurosci.org/content/23/26/8903.abstract
AB 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 P2X2(P2X3)2.