Evidence map›Paper›PMID 41290683›Full record

ArticleNature communications2025

Substrate recognition diversity and transport dynamics of ABCC1.

Panpan Sun, Kexin Liu, Linnan Zhang, Qixiang Zhang, Yina Gao, Zhaolong Li, Yalan Zhu, Songqing Liu, Liguo Zhang, Ang Gao and 1 more

Abstract read
PubMed Full text at PMC Publisher
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

11 authors.

Panpan Sun *National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.ORCID http://orcid.org/0000-0002-5931-478X
Kexin Liu *National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.ORCID http://orcid.org/0009-0007-4413-0439
Linnan Zhang *Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
Qixiang ZhangSchool of Life Sciences, Beijing Institute of Technology, Beijing, China.ORCID http://orcid.org/0000-0001-7879-171X
Yina GaoNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Zhaolong LiNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Yalan ZhuSchool of Life Sciences, Beijing Institute of Technology, Beijing, China.
Songqing LiuNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Liguo ZhangNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.ORCID http://orcid.org/0000-0002-9795-0314
Ang GaoSchool of Life Sciences, Beijing Institute of Technology, Beijing, China.ORCID http://orcid.org/0000-0001-8834-9781
Pu GaoNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. gaopu@ibp.ac.cn.ORCID http://orcid.org/0000-0002-5328-9755

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32325028
6 · The paper itself

Abstract

ABCC1 is an ATP-binding cassette (ABC) transporter that exports diverse endogenous and exogenous substrates, conferring resistance to many anticancer drugs and mediating various physiological functions. Here, we present ten cryo-EM structures of ABCC1 in different functional states, providing systematic insights into its substrate recognition diversity and transport dynamics. ABCC1 utilizes a plastic bipartite substrate-binding pocket and a substrate-induced conformational flexibility to accommodate molecules with diverse properties, including bimolecular glutathione (GSH)-substrate pairs, GSH conjugates, and GSH-independent cyclic dinucleotides. A herein characterized substrate-releasing intermediate state reveals ATP-mediated overall conformational transitions and detailed pocket reorganization during substrate loading, pre-release, and post-release. Unexpectedly, we identify a sequential nucleotide release mechanism where the hydrolysis product ADP, rather than unhydrolyzed ATP, releases first, priming the transporter for turnover and resetting. Complemented by mutagenesis and functional assays, these findings provide a complete framework for understanding ABCC1's molecular basis and offer a foundation for developing next-generation modulators.

Indexed as

ATP-Binding Cassette, Sub-Family C ProteinsAdenosine DiphosphateAdenosine TriphosphateBinding SitesBiological TransportCryoelectron MicroscopyGlutathioneHumansHydrolysisModels, MolecularProtein BindingProtein ConformationSubstrate SpecificityAdenosine DiphosphateAdenosine TriphosphateATP-Binding Cassette, Sub-Family C ProteinsGlutathionemultidrug resistance-associated protein 1

Identifiers

PMID41290683
PMCPMC12647609

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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 OpenQuestion graph.