Trimeric architecture of homomeric P2X2 and heteromeric P2X1+2 receptor subtypes.
Of the three major classes of ligand-gated ion channels, nicotinic receptors and ionotropic glutamate receptors are known to be organized as pentamers and tetramers, respectively. The architecture of the third class, P2X receptors, is under debate, although evidence for a trimeric assembly is accumulating. Here we provide biochemical evidence that in addition to the rapidly desensitising P2X1 and P2X3 receptors, the slowly desensitising subtypes P2X2, P2X4, and P2X5 are trimers of identical subunits. Similar (heteromeric) P2X subunits also formed trimers, as shown for co-expressed P2X1 and P2X2 subunits, which assembled efficiently to a P2X1+2 receptor that was exported to the plasma membrane. In contrast, P2X6 subunits, which are incapable of forming functional homomeric channels in Xenopus oocytes, were retained in the ER as apparent tetramers and high molecular mass aggregates. Altogether, we conclude from these data that a trimeric architecture is the structural hallmark of functional homomeric and heteromeric P2X receptors.
Aschrafi
Armaz
A
Department of Molecular Pharmacology, Technical University of Aachen, Wendlingweg 2, D-52074, Germany.
Sadtler
Sven
S
Niculescu
Cristina
C
Rettinger
Jürgen
J
Schmalzing
Günther
G
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000737:chemistry* / Q000378:metabolism; D058469:Receptors, Purinergic P2X; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D058848:Receptors, Purinergic P2X4; D058485:Receptors, Purinergic P2X5; D014982:Xenopus laevis
C546401:P2RX2 protein, human; C546407:P2RX3 protein, human; C548226:P2RX4 protein, human; C546465:P2RX5 protein, human; D021122:Protein Subunits; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D058848:Receptors, Purinergic P2X4; D058485:Receptors, Purinergic P2X5; C110590:purinoceptor P2X6