Evidence map›Paper›PMID 41381453›Full record

ArticleNature communications2025

Structural basis of PANX1 permeation and positive modulation by mefloquine.

Yangyang Li, Zheng Ruan, Junuk Lee, Ian J Orozco, Edward Zhou, Juan Du, Wei Lü

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 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Nicotinamide-Based Covalent Inhibitors of tRNA (mACS medicinal chemistry letters · 2026
    Article
  3. Article
  4. Article
  5. 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

7 authors.

Yangyang Li *Department of Molecular Biosciences, Northwestern University, Evanston, IL, USA.
Zheng Ruan *Department of Structural Biology, Van Andel Institute, Grand Rapids, MI, USA.ORCID http://orcid.org/0000-0002-4412-4916
Junuk LeeDepartment of Molecular Biosciences, Northwestern University, Evanston, IL, USA.
Ian J OrozcoDepartment of Structural Biology, Van Andel Institute, Grand Rapids, MI, USA.
Edward ZhouDepartment of Molecular Biosciences, Northwestern University, Evanston, IL, USA.
Juan DuDepartment of Molecular Biosciences, Northwestern University, Evanston, IL, USA. juan.du@northwestern.edu.ORCID http://orcid.org/0000-0003-1467-1203
Wei LüDepartment of Molecular Biosciences, Northwestern University, Evanston, IL, USA. wei.lu@northwestern.edu.ORCID http://orcid.org/0000-0002-3009-1025

Funding

Structural and Functional Studies of the TRPM4 and TRPM5 ChannelsR01HL153219 · NHLBI · VAN ANDEL RESEARCH INSTITUTE · PI Wei Lu · 2020 to 2026
$3.9M
Structural Basis of Nociceptor Channel TRPM3 gating and pharmacologyR01NS129804 · NINDS · VAN ANDEL RESEARCH INSTITUTE · PI Juan Du · 2023 to 2026
$2.8M
Structural and functional studies of the TRPM2 channelR01NS111031 · NINDS · VAN ANDEL RESEARCH INSTITUTE · PI DU, JUAN · 2019 to 2023
$2.7M
Structural and functional studies of CALHM channelsR01NS112363 · NINDS · VAN ANDEL RESEARCH INSTITUTE · PI LU, WEI · 2020 to 2024
$2.3M
Elucidating structures and molecular mechanisms of Pannexin channelsR35GM138321 · NIGMS · VAN ANDEL RESEARCH INSTITUTE · PI LU, WEI · 2020 to 2024
$2.3M
Structural and Functional Studies on Proton-activated Chloride (PAC) ChannelR00NS128258 · NINDS · THOMAS JEFFERSON UNIVERSITY · PI Zheng Ruan · 2024 to 2026
$740k
American Heart Association (American Heart Association, Inc.) 20POST35120556NHLBI NIH HHS R01 HL153219NIGMS NIH HHS R35 GM138321NINDS NIH HHS R00 NS128258NINDS NIH HHS R01 NS111031NINDS NIH HHS R01 NS112363NINDS NIH HHS R01 NS129804U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL153219U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM138321U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R00NS128258U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS111031U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS112363U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS129804
6 · The paper itself

Abstract

Purinergic signaling relies on ATP release through exocytosis and large-pore channels. Large-pore channels permeate both small anions like chloride and large signaling molecules like ATP, but how this broad cargo selectivity is structurally controlled remains elusive. Here we investigate PANX1, a prototypical large-pore channel, and uncover structural plasticity at the extracellular entrance formed by seven tryptophan (W74) residues. The W74 sidechains are flexible, sampling conformations that range from a constricted state permissive only to chloride to a dilated state compatible with ATP. These states are coupled to variable cation-π interactions between W74 and arginine 75 (R75), suggesting a mechanism for dynamic tuning of pore architecture and selective cargo permeation. We also identify mefloquine as a positive modulator of PANX1 that binds near the side tunnel to control ion flow through this pathway. Together, these findings define the structural principles underlying PANX1 permeation and modulation.

Indexed as

ConnexinsMefloquineNerve Tissue ProteinsAdenosine TriphosphateAnimalsHumansProtein ConformationTryptophanAdenosine TriphosphateConnexinsMefloquineNerve Tissue ProteinsPANX1 protein, humanTryptophan

Identifiers

PMID41381453
PMCPMC12698695

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.