Evidence map›Paper›PMID 40670814›Full record

ArticleNature structural & molecular biology2025

Structural basis of ClC-3 transporter inhibition by TMEM9 and PtdIns(3,5)P

Marina Schrecker, Yeeun Son, Rosa Planells-Cases, Sumanta Kar, Viktoriia Vorobeva, Uwe Schulte, Bernd Fakler, Thomas J Jentsch, Richard K Hite

Abstract read
In one paragraph

Article in Nature structural & molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Ion transport as a determinant of membrane fusion and fission.Nature structural & molecular biology · 2026
    Review
  2. Article
  3. Review
  4. Article
  5. Subcellular Cartography of the Phosphoinositide Multiverse.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026
    Review
  6. Article
  7. Quantitative comparison of PI(3,5)PbioRxiv : the preprint server for biology · 2025
    Article
  8. Article
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Marina Schrecker *Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Yeeun Son *Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-3324-7635
Rosa Planells-CasesLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.ORCID http://orcid.org/0000-0002-9841-8434
Sumanta KarLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.ORCID http://orcid.org/0000-0002-3368-8986
Viktoriia VorobevaLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.ORCID http://orcid.org/0009-0004-1977-2120
Uwe SchulteInstitute of Physiology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0003-3557-0591
Bernd FaklerInstitute of Physiology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0001-7264-6423
Thomas J JentschLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany. Jentsch@fmp-berlin.de.ORCID http://orcid.org/0000-0002-3509-2553
Richard K HiteStructural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. hiter@mskcc.org.ORCID http://orcid.org/0000-0003-0496-0669

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Michael Jason de la Cruz · 1985 to 2026
$347.4M
Mechanisms of lysosomal ion transport proteins involved in pH homeostasisR01GM141553 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI HITE, RICHARD KEVIN · 2022 to 2025
$1.8M
Molecular mechanisms of protein functionR35GM156616 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI Richard Kevin Hite · 2025 to 2026
$1.3M
NCI NIH HHS P30 CA008748NIGMS NIH HHS R01 GM141553NIGMS NIH HHS R35 GM156616
6 · The paper itself

Abstract

The trafficking and activity of endosomes relies on the exchange of chloride ions and protons by members of the CLC family of chloride channels and transporters; mutations of the genes encoding these transporters are associated with numerous diseases. Despite their critical roles, the mechanisms by which CLC transporters are regulated are poorly understood. Here we show that two related accessory β-subunits, TMEM9 and TMEM9B, directly interact with ClC-3, ClC-4 and ClC-5. Cryo-electron microscopy structures reveal that TMEM9 inhibits ClC-3 by sealing the cytosolic entrance to the Cl

Indexed as

Chloride ChannelsPhosphatidylinositol PhosphatesAnimalsChloridesCryoelectron MicroscopyEndosomesHEK293 CellsHumansModels, MolecularProtein BindingChloride ChannelsChloridesClC-3 channelphosphatidylinositol 3,5-diphosphatePhosphatidylinositol Phosphates

Identifiers

PMID40670814
PMCPMC12403049

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.