Structural studies of transient receptor potential channels (TRPs) using molecular modeling and dynamic simulation / Wan Dalila Wan Chik

Transient Receptor Potential Canonical (TRPC) channel was the first group of TRP homologs that was cloned in mammals. The channel consists of seven subfamily members in this family. TRPC4 channels are nonselective cation channels permeable to Ca2+ that are expressed in various organs and cell types including numerous types of neurons, cardiovascular system, skeletal muscle cells, kidney, and immune cells. TRPC4 channels assemble into a tetrameric structure in the plasma membrane. The S4- S5 linker of TRPC4 has been shown to regulate the open-close of the channel by interacting with the S6 helix. Previous homology models that were built based on the potassium channel structure predicted inter-domain interactions were formed by G503 and the S623 between the linker with the S6 helix. Mutagenesis experiments of TRPC4 and TRPC5 supported that the mutation of the conserved glycine impaired the interaction, which resulted to the channel opening, and causing cell death due to the influx of Ca2+.