Conservation and divergence of structure in 6-TM cation channels. (A) Conserved architecture of tetrameric 6-TM channels. Four helix–reentrant–loop helix pore domains (S5–pore–S6 helices) assemble like staves of a barrel to form an ion-conducting pore. The S1–S4 helices form isolated sensor domains around the periphery of the pore. Viewed from above, helices are represented as circles and colored to distinguish different subunits. (B) Structure of a representative TRP channel subunit (TRPV1). Pink helices mark the TM core. TRPV1 contains an intracellular domain and an ankyrin repeat domain, but other TRP channels contain coiled-coils, subfamily-specific regions, and even soluble enzymes. (C) Structure of a Shaker-type Kv channel subunit (the Kv1.2/2.1 paddle chimera). Blue helices mark the TM core. Kv channels feature different intracellular domains than TRP channels.