Tlie long term goal of this study is to elucidate tfie molecular mechanisms underlying P2X receptor functions by combining structural and functional approaches. P2X receptors are trimeric ATP-gated ion channels that are widely distributed throughout the human body. Activation of these receptors causes cation influx that evokes action potentials or triggers calcium mediated signaling, important functions in signal transmission, inflammation, and pain sensation. While the first crystal structure in its closed state provides a number of novel insights into receptor architecture, mechanisms of P2X receptor functions are largely unknown. To determine the cation selection mechanism and the structural changes during gating, two specific aims are designed as follows;1) to identify the ion selection machinery using patch clamp recording techniques, and 2) to localize ion binding sites and determine the crystal structure in the open state using X-ray crystallography. Completion of these studies is expected to provide the first compelling mechanisms and structural basis for the cation selectivity, which may in turn lead to the design of novel pharmacological agents targeting P2X receptors.
;. P2X receptors are ion channels widely distributed throughout the human body and play important roles in inflammatory response and pain sensation. My research objective is to understand meehahisrris of how P2X receptors function at a mdlecular level, which may lead to the design of novel pharmacological agents to treat inflammatory diseases and to relieve pain.
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|Karasawa, Akira; Kawate, Toshimitsu (2016) Structural basis for subtype-specific inhibition of the P2X7 receptor. Elife 5:|
|Kawate, Toshimitsu; Robertson, Janice L; Li, Mufeng et al. (2011) Ion access pathway to the transmembrane pore in P2X receptor channels. J Gen Physiol 137:579-90|