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	TRPML2 in distinct states reveals the activation and modulation principles of the TRPML family.
Journal, issue, pages	Nat Commun, Vol. 16, Issue 1, Page 5325, Year 2025
Publish date	Jun 17, 2025
Authors	Philip Schmiege / Dawid Jaślan / Michael Fine / Nidish Ponath Sadanandan / Alexandra Hatton / Nadia Elghobashi-Meinhardt / Christian Grimm / Xiaochun Li /
PubMed Abstract	TRPML2 activity is critical for endolysosomal integrity and chemokine secretion, and can be modulated by various ligands. Interestingly, two ML-SI3 isomers regulate TRPML2 oppositely. The molecular ...TRPML2 activity is critical for endolysosomal integrity and chemokine secretion, and can be modulated by various ligands. Interestingly, two ML-SI3 isomers regulate TRPML2 oppositely. The molecular mechanism underlying this unique isomeric preference as well as the TRPML2 agonistic mechanism remains unknown. Here, we present six cryo-EM structures of human TRPML2 in distinct states revealing that the π-bulge of the S6 undergoes a π-α transition upon agonist binding, highlighting the remarkable role of the π-bulge in ion channel regulation. Moreover, we identify that PI(3,5)P allosterically affects the pose of ML2-SA1, a TRPML2 specific activator, resulting in an open channel without the π-α transition. Functional and structural studies show that mutating the S5 of TRPML1 to that of TRPML2 enables the mutated TRPML1 to be activated by (+)ML-SI3 and ML2-SA1. Thus, our work elucidates the activation mechanism of TRPML channels and paves the way for the development of selective TRPML modulators.
External links	Nat Commun / PubMed:40527873 / PubMed Central
Methods	EM (single particle)
Resolution	2.35 - 3.01 Å
Structure data	48135 9eks EMDB-48135, PDB-9eks: ML2-SA1 bound TRPML1-V432A/A433G in a partially open state Method: EM (single particle) / Resolution: 2.42 Å 48136 9ekt EMDB-48136, PDB-9ekt: (+)ML-SI3 bound TRPML1-V432A/A433G in a partially open state Method: EM (single particle) / Resolution: 2.35 Å 48137 9eku EMDB-48137, PDB-9eku: (+)ML-SI3 bound TRPML1-V432A/A433G in a pre-open state Method: EM (single particle) / Resolution: 2.68 Å 48138 9ekv EMDB-48138, PDB-9ekv: ML-SA5 bound TRPML1 in an open state Method: EM (single particle) / Resolution: 2.75 Å 48139 9ekw EMDB-48139, PDB-9ekw: Apo TRPML2 in a closed state Method: EM (single particle) / Resolution: 3.01 Å 48140 9ekx EMDB-48140, PDB-9ekx: (-)ML-SI3 bound TRPML2 in a closed state Method: EM (single particle) / Resolution: 2.6 Å 48141 9eky EMDB-48141, PDB-9eky: (+)ML-SI3 bound TRPML2 in a pre-open state Method: EM (single particle) / Resolution: 2.67 Å 48142 9ekz EMDB-48142, PDB-9ekz: (+)ML-SI3 bound TRPML2 in an open state Method: EM (single particle) / Resolution: 2.61 Å 48143 9el0 EMDB-48143, PDB-9el0: ML2-SA1 bound TRPML2 in a pre-open state Method: EM (single particle) / Resolution: 2.45 Å 48144 9el1 EMDB-48144, PDB-9el1: ML2-SA1/PI(3,5)P2 bound TRPML2 in an open state Method: EM (single particle) / Resolution: 2.61 Å
Chemicals	PDB-1bi6: NMR STRUCTURE OF BROMELAIN INHIBITOR VI FROM PINEAPPLE STEM ChemComp-ZB4: N-{(1S,2S)-2-[4-(2-methoxyphenyl)piperazin-1-yl]cyclohexyl}benzenesulfonamide / channel blocker, antagonistYM PDB-1ivc: STRUCTURES OF AROMATIC INHIBITORS OF INFLUENZA VIRUS NEURAMINIDASE PDB-1iv3: Structure of 2C-Methyl-D-erythritol-2,4-cyclodiphosphate Synthase (bound form MG atoms) 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
Source	homo sapiens (human)
Keywords	TRANSPORT PROTEIN / TRPML / calcium channel / ion transport / cryo-EM / MEMBRANE PROTEIN