Research groups at the University of Tokyo, National Institute of Advanced Industrial Science and Technology, and University of Tsukuba have succeeded for the first time in the world in measuring the internal motion of one molecule of the TRP channel, which controls heat and pain transmission, in real time on the order of microseconds.It is expected to contribute to understanding the pain recognition mechanism and the development of new analgesics.
TRP channels are composed of four subunits (secondary units of proteins), which are molecules that penetrate the cell membrane 4 times and are known to be involved in the response of multiple sensory stimuli in humans and various animal species.Recently, the detailed molecular structure has been determined, and research has been further accelerated and attracted attention.However, due to the complex molecular structure, no one has succeeded in measuring the real-time motion associated with channel opening and closing.
This time, we conducted an experiment in which capsaicin that activates TRP channels was added.The movement of opening the channel and flowing ions was accompanied by a clockwise twisting motion, and in the experiment in which a drug that inhibits the channel was added, a counterclockwise twisting motion was detected.Furthermore, in experiments using mutant TRP channels that do not respond to capsaicin, counterclockwise twisting motion that suppresses the movement of the channel was detected as when the inhibitor was added.In this way, we succeeded in detecting dynamic movement in real time under various conditions.It was also found that all of these movements move with an extremely small diffusion constant (a constant representing the magnitude of Brownian motion) of several tens of pm1 (square picometers) per millisecond.
Since TRP channels are closely related to the mechanism of pain in humans, these results are expected to be useful for understanding the pain recognition mechanism and developing new analgesics.In addition, among the 27 types of TRP channels, there are many molecules that are closely related to the onset of diseases, and the development of therapeutic agents is expected.
Paper information:[The Journal of Physical Chemistry] Agonist and antagonist diverted twisting motions of single TRPV1 channel