抄録
The crystal structure analyses of ion channels had been awaited for a long time to elucidate the structure-function relationship, but the application was limited by the difficulty of crystallization of membrane proteins. Significant progresses were made in the last ten years by MacKinnon's and other groups, and many important findings such as the structural basis of K+ selectivity in K+ channels have been reported. These facts prove the undoubted effectiveness of the structural biological approach to the ion channel research. It is also true, however, that there are many important questions remaining unanswered even after the initial crystal structural analysis. These include dynamic aspects of structural rearrangements, environment dependent changes, and formation and function of channel complexes. Our group aims to know the dynamic aspect of membrane proteins in function towards the elucidation of functioning mechanisms. In this presentation, I would like to first introduce very briefly three topics from our previous works: (1) FRET approach to the structural rearrangements of metabotropic glutamate receptor1; (2) Density dependent changes of pore properties of ATP receptor channel P2X2; (3) Voltage and [ATP] dependent gating of P2X2 which lacks voltage sensor. I will then introduce in detail our recent work using cys accessibility analysis focusing on (4) the effect of accessory subunit KCNE1 and KCNE3 on the movement of voltage sensor of KCNQ1 channel, which gives insight into how the assembly of KCNE1 and 3 modifies the activation of KCNQ1 channel. [J Physiol Sci. 2008;58 Suppl:S25]
