Structure and function of KCNH channels

As part of a long-standing collaboration with Joao Morais-Cabral and his colleagues in Porto, Portugal, we are using structural, biochemical and physiological analyses to understand the interactions of proteins and protein domains at the molecular and atomic levels. What distinguishes KCNH from other types of voltage-gated potassium channels are highly conserved cytoplasmic domains in the N and C termini of the channel subunits. Thanks to structural studies by Bill Zagotta, Rod Mackinnon and others, we know that the N-terminal “PAS” domain interacts with C-terminal domains of neighboring subunits. The C-terminal domains have homology to cyclic nucleotide-binding domains of channels gated by cyclic nucleotides, but in KCNH channels these domains are intrinsically liganded by a downstream segment of the channel protein. A recent paper in JGP (below) shows how important the structure of this interaction is for channel gating.