Evidence map›Paper›PMID 40527873›Full record

ArticleNature communications2025

TRPML2 in distinct states reveals the activation and modulation principles of the TRPML family.

Philip Schmiege, Dawid Jaślan, Michael Fine, Nidish Ponath Sadanandan, Alexandra Hatton, Nadia Elghobashi-Meinhardt, Christian Grimm, Xiaochun Li

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Philip Schmiege *Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0001-5703-7806
Dawid Jaślan *Department of Pharmacology and Toxicology, Medical Faculty, Ludwig Maximilian University of Munich, Munich, Germany.ORCID http://orcid.org/0000-0002-0685-7633
Michael FineDepartment of Biology, Bowdoin College, Brunswick, ME, USA.
Nidish Ponath SadanandanImmunology, Infection and Pandemic Research IIP, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Munich/Frankfurt, Germany.
Alexandra HattonDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nadia Elghobashi-MeinhardtSchool of Chemistry, University College Dublin, South Belfield Dublin 4, Dublin, Ireland.
Christian GrimmDepartment of Pharmacology and Toxicology, Medical Faculty, Ludwig Maximilian University of Munich, Munich, Germany. Christian.Grimm@med.uni-muenchen.de.ORCID http://orcid.org/0000-0002-0177-5559
Xiaochun LiDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA. xiaochun.li@utsouthwestern.edu.ORCID http://orcid.org/0000-0002-0177-0803

Funding

TRANSCRIPTIONAL REGULATION OF LDL RECEPTOR PROMOTERP01HL020948 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI GOLDSTEIN, JOSEPH L · 1985 to 2021
$103.1M
Tissue Culture & Antibody Production CoreP01HL160487 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI Helen Haskell Hobbs · 2022 to 2026
$14.9M
UT Southwestern NORCP30DK127984 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI Jeff G McDonald · 2022 to 2026
$7.4M
Structural and Functional Investigations on Cholesterol Signaling and MetabolismR35GM149533 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI Xiaochun Li · 2023 to 2026
$1.9M
G. Harold and Leila Y. Mathers Foundation (G. Harold & Leila Y. Mathers Foundation) MF-2302-03702NHLBI NIH HHS P01 HL020948NIDDK NIH HHS P30 DK127984NIGMS NIH HHS R35 GM149533U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) P01HL160487U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM149533Welch Foundation I-1957
6 · The paper itself

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 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

Indexed as

Transient Receptor Potential ChannelsAllosteric RegulationCryoelectron MicroscopyHEK293 CellsHumansModels, MolecularTransient Receptor Potential Channels

Identifiers

PMID40527873
PMCPMC12174366

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.