Subunit stoichiometry and channel pore structure of ion channels: all for one, or one for one?

摘要

Ion channels are macromolecular protein complexes that open and close their pores to control rapid ion fluxes across the cell membranes (Hille, 2001). In general, a single ion-conducting pore is usually formed at the central axis by symmetrical assembly of homologous structural units, either in multimeric pore-forming subunits or internal repeats of a single pore-forming polypeptide. Based on the stoichiometry of structural units surrounding the channel pore (Unwin, 1989; Hille, 2001), most known ion channels can be categorized into classes of three, four, five and six structural units (Fig. 1A). Recent biochemical analysis and atomic force microscopy imaging suggest that P2X receptors contain three subunits. The voltage-gated Na+, K+ and Ca2+ channels, inositol 1,4,5-trisphosphate receptor and ryanodine receptor Ca2+ release channels, HCN channels, CNG channels, TRP channels, and ionotropic glutamate receptors share the four-unit stoichiometry. Some ligand-gated receptors such as nicotinic acetylcholine receptors, GABAA receptors and glycine receptors belong to the five-unit class, while the gap junction channels fit into the six-unit class.