Reply to Yao et al.: Is the pore turret just thermoTRP channels’ appendix?

Abstract

Numerous studies of thermosensitive transient receptor potential (thermoTRP) channels have focused on the outer pore that contains sites critical for the channel's sensitivity to temperature, acidification, spider toxin, and other gating modulators (Fig. 1). Two segments of each subunit contribute to the outer pore structure: one is between S5 and the pore helix, the other is between the selectivity filter and S6. For the convenience of discussion, we call them the large turret and the small turret, respectively. From the available structural information of tetrameric channels, it is expected that the two turrets interact extensively. Indeed, the sites affecting gating spread across the outer pore landscape. Of particular interests are a number of sites that when mutated, lead to permanent opening or closing of the temperature-activation gate (1–3).