Swapping of transmembrane domains in the epithelial calcium channel TRPV6

Tetrameric ion channels have either swapped or non-swapped arrangements of the S1–S4 and pore domains. Here we show that mutations in the transmembrane domain of TRPV6 can result in conversion from a domain-swapped to non-swapped fold. These results reveal structural determinants of domain swapping and raise the possibility that a single ion channel subtype can fold into either arrangement in vivo, affecting its function in normal or disease states.