Rendezvous with PI(3,5)P2-A rapalog gets caught opening TRPML1

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

Automated summary

TRPML1 is an endolysosomally-expressed cation channel, activated by PI(3,5)P-2 and synthetic agonists like rapamycin. New high resolution cryo-EM structures of TRPML1 bound to both PI(3,5)P-2 and temsirolimus reveal molecular insights into how the channel integrates two agonists at distal sites but cooperatively.