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

Cell Calcium. 2022 Jul:105:102597. doi: 10.1016/j.ceca.2022.102597. Epub 2022 May 14.

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.

Keywords: Allosteric; Ca(2+) channels; Lysosome; PI(3,5)P(2); Rapamycin; TRPML1; Temsirolimus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Lysosomes / metabolism
  • MTOR Inhibitors
  • Sirolimus
  • Transient Receptor Potential Channels* / metabolism

Substances

  • MTOR Inhibitors
  • Transient Receptor Potential Channels
  • Sirolimus