Towards a structural view of drug binding to hERG K+ Channels

The human ether-a-go-go-related gene (hERG) K + channel is of great medical and pharmaceutical relevance. Inherited mutations in hERG result in congenital long-QT syndrome which is associated with a markedly increased risk of cardiac arrhythmia and sudden death. hERG K + channels are also remarkably susceptible to block by a wide range of drugs, which in turn can cause drug-induced long-QT syndrome and an increased risk of sudden death. The recent determination of the near-atomic resolution structure of the hERG K + channel, using single-particle cryo-electron microscopy (cryo-EM), provides tremendous insights into how these channels work. It also suggests a way forward in our quest to understand why these channels are so promiscuous with respect to drug binding. Background to hERG K + channels and drug-induced cardiac arrhythmias.The first near-atomic level view of the hERG K + channel solved using single particle cryo-EM.Insights into the structural basis of function and drug binding to hERG K + channels.The presence of hydrophobic pouches sprouting from the central cavity provides a plausible explanation for the promiscuity of drug binding to hERG K + channels.