Structure of the Thermo-Sensitive TRP Channel TRP1 from the Alga Chlamydomonas Reinhardtii
Published on 09.16.2019 in Nature Communications
Luke L. McGoldrick, Appu K. Singh, Lusine Demirkhanyan, Ting-Yu Lin, Ryan G. Casner, Eleonora Zakharian, Alexander I. Sobolevsky
Algae produce the largest amount of oxygen on earth and are invaluable for human nutrition and biomedicine, as well as for the chemical industry, energy production and agriculture. The mechanisms by which algae can detect and respond to changes in their environments can rely on membrane receptors, including transient receptor potential (TRP) ion channels. We have solved 3.5-Å resolution cryo-EM structures of the TRP channel crTRP1 from the alga Chlamydomonas reinhardtii in MSP2N2/lipid nanodiscs and in the detergent GDN. re
The structure of crTRP1 has a unique 2-fold symmetrical rose-shape architecture with elbow domains and ankyrin repeat domains submerged and dipping into the membrane, respectively. The fold and architecture of the crTRP1 structure are significantly different from those of other TRP channel structures determined previously.
crTRP1 is highly heat-sensitive and requires both increased temperature and the presence of phosphoinositides (for example, phosphatidylinositol-4,5-bisphosphate PIP2 or phosphatidylinositol-4-phosphate PI(4)P) for activation. Fitting of the strong Po temperature dependence yielded a high temperature coefficient, Q10 = 25, comparable to the Q10 for the temperature sensitive mammalian TRP channels TRPM8 and TRPV1.
We identified 4 types of non-protein densities in the transmembrane region of crTRP1 cryo-EM map: one in the central pore and three at the protein-lipid interfaces. Site 1 and 2 densities were modeled as PIP2 and site 3 density as phosphatidylcholine (PC).
This study provides the first structure of a TRP channel from a micro-organism and a structural framework for better understanding algae biology and TRP channel evolution.
This work was done in collaboration with Dr. Zakharian group, University of Illinois College of Medicine Peoria.