Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural mechanism of allosteric activation of TRPML1 by PI(3,5)P and rapamycin.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 119, Issue 7, Year 2022
Publish date	Feb 15, 2022
Authors	Ninghai Gan / Yan Han / Weizhong Zeng / Yan Wang / Jing Xue / Youxing Jiang /
PubMed Abstract	Transient receptor potential mucolipin 1 (TRPML1) is a Ca-permeable, nonselective cation channel ubiquitously expressed in the endolysosomes of mammalian cells and its loss-of-function mutations are ...Transient receptor potential mucolipin 1 (TRPML1) is a Ca-permeable, nonselective cation channel ubiquitously expressed in the endolysosomes of mammalian cells and its loss-of-function mutations are the direct cause of type IV mucolipidosis (MLIV), an autosomal recessive lysosomal storage disease. TRPML1 is a ligand-gated channel that can be activated by phosphatidylinositol 3,5-bisphosphate [PI(3,5)P] as well as some synthetic small-molecule agonists. Recently, rapamycin has also been shown to directly bind and activate TRPML1. Interestingly, both PI(3,5)P and rapamycin have low efficacy in channel activation individually but together they work cooperatively and activate the channel with high potency. To reveal the structural basis underlying the synergistic activation of TRPML1 by PI(3,5)P and rapamycin, we determined the high-resolution cryoelectron microscopy (cryo-EM) structures of the mouse TRPML1 channel in various states, including apo closed, PI(3,5)P-bound closed, and PI(3,5)P/temsirolimus (a rapamycin analog)-bound open states. These structures, combined with electrophysiology, elucidate the molecular details of ligand binding and provide structural insight into how the TRPML1 channel integrates two distantly bound ligand stimuli and facilitates channel opening.
External links	Proc Natl Acad Sci U S A / PubMed:35131932 / PubMed Central
Methods	EM (single particle)
Resolution	2.11 - 2.598 Å
Structure data	25377 7sq6 EMDB-25377, PDB-7sq6: Cryo-EM structure of mouse agonist ML-SA1-bound TRPML1 channel at 2.32 Angstrom resolution Method: EM (single particle) / Resolution: 2.32 Å 25378 7sq7 EMDB-25378, PDB-7sq7: Cryo-EM structure of mouse PI(3,5)P2-bound TRPML1 channel at 2.41 Angstrom resolution Method: EM (single particle) / Resolution: 2.41 Å 25379 7sq8 EMDB-25379, PDB-7sq8: Cryo-EM structure of mouse apo TRPML1 channel at 2.598 Angstrom resolution Method: EM (single particle) / Resolution: 2.598 Å 25380 7sq9 EMDB-25380, PDB-7sq9: Cryo-EM structure of mouse temsirolimus/PI(3,5)P2-bound TRPML1 channel at 2.11 Angstrom resolution Method: EM (single particle) / Resolution: 2.11 Å
Chemicals	ChemComp-AQV: 2-{2-oxo-2-[(4S)-2,2,4-trimethyl-3,4-dihydroquinolin-1(2H)-yl]ethyl}-1H-isoindole-1,3(2H)-dione ChemComp-NA: Unknown entry ChemComp-HOH: WATER / Water ChemComp-EUJ: (2R)-3-{[(S)-hydroxy{[(1S,2R,3R,4S,5S,6R)-2,4,6-trihydroxy-3,5-bis(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propane-1,2-diyl dioctanoate ChemComp-A4I: (1R,2R,4S)-4-{(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,30S,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontin-3-yl]propyl}-2-methoxycyclohexyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate / Temsirolimus
Source	mus musculus (house mouse)
Keywords	MEMBRANE PROTEIN / ion channel