Hot on the Trail of TRP Channel Structure

The transient receptor potential (TRP) family of proteins are generally nonselective cation channels that participate in many sensory and physiological processes. To date, no structural information at the atomic level is available for any full-length TRP channels due to difficulties encountered in overexpression, functional purification, and crystallization of eukaryotic transmembrane proteins. However, progress toward obtaining TRP protein structures has been made by combining different techniques, such as cryoelectron microscopy of entire proteins, x-ray crystallography of isolated cytosolic domains, and extensive mutagenesis combined with functional assays in heterologous expression systems. This perspective focuses on recent developments in the determination of TRP channel structure by electron cryomicroscopy and single-particle analysis, and the use of multi-resolution and divide and conquer approaches to solving this problem. It also discusses the implications of new methods for expression and purification for future prospects in two-and three-dimensional crystallography, as well as the use of biophysical techniques to assess the functionality of purified TRP proteins that are used for structural analysis, and to study their direct interactions with other proteins.