Evidence of absence with a twist: voltage-operated Ca2+ channel β subunit in T cells

Abstract

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.