Rendezvous with PI(3, 5)P2 — A rapalog gets caught opening TRPML1. (July 2022)

• Record Type: Journal Article
• Authors: Rahman, Taufiq; Patel, Sandip
• Is Part Of: Cell calcium. Volume 105(2022)
• Publication Date: 2022-07
• Subjects: TRPML1 -- PI(3, 5)P2 -- Rapamycin -- Allosteric -- Temsirolimus -- Lysosome -- Ca2+ channels; Calcium -- Metabolism -- Periodicals; Vertebrates -- Physiology -- Periodicals; Calcium -- Physiological effect -- Periodicals; Cell physiology -- Periodicals; Calcium in the body -- Periodicals; 572.516
• DOI: 10.1016/j.ceca.2022.102597
• Languages: English
• ISSNs: 0143-4160

Abstract

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.