Evidence map›Paper›PMID 40328781›Full record

ArticleNature communications2025

Revealing the location and dynamics of a concealed binding site in the dopamine transporter.

Rong Zhu, Walter Sandtner, Thomas Stockner, Alexander Heilinger, Marion Holy, Oliver Kudlacek, Linda Wildling, Kusumika Saha, Anna Sophie Fröhlich, Michael Bindl and 13 more

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 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
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

23 authors.

Rong Zhu *Institute of Biophysics, Johannes Kepler University Linz, Linz, Austria. rong.zhu@jku.at.ORCID http://orcid.org/0000-0001-7553-7249
Walter Sandtner *Institute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0003-3637-260X
Thomas Stockner *Institute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0002-7071-8283
Alexander HeilingerInstitute of Biophysics, Johannes Kepler University Linz, Linz, Austria.
Marion HolyInstitute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Oliver KudlacekInstitute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Linda WildlingInstitute of Biophysics, Johannes Kepler University Linz, Linz, Austria.
Kusumika SahaInstitute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Anna Sophie FröhlichInstitute of Biophysics, Johannes Kepler University Linz, Linz, Austria.ORCID http://orcid.org/0000-0001-5911-924X
Michael BindlInstitute of Biophysics, Johannes Kepler University Linz, Linz, Austria.ORCID http://orcid.org/0000-0003-0113-7212
Paraskevi TziortzoudaInstitute of Biophysics, Johannes Kepler University Linz, Linz, Austria.
Anna HaiderInstitute of Biophysics, Johannes Kepler University Linz, Linz, Austria.
Julia GoblInstitute of Biophysics, Johannes Kepler University Linz, Linz, Austria.
Saanfor Hubert SuhInstitute of Biophysics, Johannes Kepler University Linz, Linz, Austria.
Jawad Akbar KhanInstitute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0002-6955-3282
Julia BicherInstitute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Nina KastnerInstitute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0002-1576-9029
Andreas EbnerInstitute of Biophysics, Johannes Kepler University Linz, Linz, Austria.ORCID http://orcid.org/0000-0001-5615-7590
Hermann J GruberInstitute of Biophysics, Johannes Kepler University Linz, Linz, Austria.
Michael FreissmuthInstitute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0001-9398-1765
Amy Hauck NewmanMedicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse-Intramural Research Program, Baltimore, MD, USA. anewman@intra.nida.nih.gov.ORCID http://orcid.org/0000-0002-4812-9474
Harald H SitteInstitute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria. harald.sitte@meduniwien.ac.at.ORCID http://orcid.org/0000-0002-1339-7444
Peter HinterdorferInstitute of Biophysics, Johannes Kepler University Linz, Linz, Austria. peter.hinterdorfer@jku.at.ORCID http://orcid.org/0000-0003-2583-1305

Funding

Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) P31599-B27Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) P32017Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) P33955Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) P35589Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) SFB35
6 · The paper itself

Abstract

The dopamine transporter (DAT) is linked to neuropsychiatric disorders including ADHD, Parkinson's disease, and substance use disorders. Accordingly, DAT is the target of illicit drugs and clinically important medicines. However, the number and function of ligand binding sites in DAT is enigmatic due to conflicting data from available structures and molecular pharmacology. Herein, we design force sensors with DAT ligands and measure their interaction forces with wild-type and mutated DATs, from which two distinct populations of unbinding strengths and off-rates are detected. The high-force population is reduced by V152I and S422A mutations, or by substituting Na

Indexed as

Dopamine Plasma Membrane Transport ProteinsBinding SitesHumansKineticsLigandsMutationProtein BindingDopamine Plasma Membrane Transport ProteinsLigands

Identifiers

PMID40328781
PMCPMC12056086

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.