TRPML1 is an endolysosomally-expressed cation channel, activated physiologically by PI(3,5)P2 and by several synthetic agonists including rapamycin. New high resolution cryo-EM- structures of TRPML1 bound to both PI(3,5)P2 and temsirolimus - a rapamycin analog provides molecular insight into how the channel integrates two agonists that bind to distal sites but act cooperatively.
Keywords: Allosteric; Ca(2+) channels; Lysosome; PI(3,5)P(2); Rapamycin; TRPML1; Temsirolimus.
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