Structure-Function Relationship of the Thermo-Sensitive TRP Channel TRP1 from the Alga ChlamydomonasReinhardtii

Abstract

The guidance systems of algae to their habitat and environmental changes involve temperature-sensitive Transient Receptor Potential (TRP) ion channels, which are evolutionary predecessors of their mammalian orthologs. Here, we undertook structural and functional characterization of the representative TRP channel from alga Chlamydomonas reinhardtii, crTRP1. We determined a 3.5-Å resolution cryo-EM structure of crTRP1, which deviates significantly from the structures of other TRP channels and has a unique 2-fold symmetrical rose-shape architecture with elbow domains and ankyrin repeat domains submerged and dipping into the membrane, respectively. We found that the crTRP1 function is tightly regulated by phosphoinositides. No channel openings were observed when crTRP1 was incorporated into the bilayers in the absence of phosphoinositides, while the addition of phosphatidylinositol-4,5-bisphosphate (PIP2) or phosphatidylinositol-4-phosphate PI(4)P readily evoked channel activity. The crTRP1 channel demonstrated outwardly rectifying currents, where rectification resulted from both – differences in the single-channel conductance and open probability (Po). Strikingly, crTRP1 exhibited high temperature sensitivity, similar to the mammalian temperature-sensitive TRP channels (thermoTRPs). The temperature dependence of the crTRP1 channel openings yielded a high value of the temperature coefficient, Q10 = 25 ± 1.17, that closely resembles the Q10 for the mammalian thermoTRPs. Combining the first structure of a TRP channel from a microorganism with its functional characterization, we provide a framework for better understanding of alga biology and TRP channel evolution.