A greasy business: Identification of a diacylglycerol binding site in human TRPC5 channels by cryo-EM

The transient receptor potential classical or canonical (TRPC) 5 channel is a non-selective calcium-permeable cation channel that recently emerged as a promising target for the treatment of various diseases such as mental disorders and kidney diseases. Thus, detailed insight into the structural properties of TRPC5 channels is of utmost importance to further advance TRPC5 channels as drug targets. Recently, Song et al. (2021) have presented cryoEM structures of the human TRPC5 channel alone or in complex with two different inhibitors thereby revealing two new distinct drug binding sites. Moreover, a binding site for the second messenger diacylglycerol (DAG) has been identified commensurate with a key role of DAG for TRPC5 channel activation.

Automated summary

The TRPC5 channel, a non-selective calcium-permeable cation channel, has emerged as a promising target for treating mental disorders and kidney diseases. Recent research has revealed the structural properties of TRPC5 channels, identified new drug binding sites, and highlighted the key role of the second messenger DAG in TRPC5 channel activation.