Evidence map›Paper›PMID 38844452›Full record

ArticleNature communications2024

Inhibition and transport mechanisms of the ABC transporter hMRP5.

Ying Huang, Chenyang Xue, Ruiqian Bu, Cang Wu, Jiachen Li, Jinqiu Zhang, Jinyu Chen, Zhaoying Shi, Yonglong Chen, Yong Wang and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. An Emerging Paradigm for ABCC5/MRP5 Function in Human Physiology.International journal of molecular sciences · 2025
    Review
  5. Review
  6. Article
  7. 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

11 authors.

Ying Huang *Shenzhen Key Labortory of Biomolecular Assembling and Regulation, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China.
Chenyang Xue *Shenzhen Key Labortory of Biomolecular Assembling and Regulation, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China.ORCID http://orcid.org/0000-0002-9603-3426
Ruiqian Bu *Shenzhen Key Labortory of Biomolecular Assembling and Regulation, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China.
Cang Wu *Shenzhen Key Labortory of Biomolecular Assembling and Regulation, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China.ORCID http://orcid.org/0000-0002-6218-8569
Jiachen LiCollege of Life Sciences, Zhejiang University, Hangzhou, 310027, China.
Jinqiu ZhangCollege of Life Sciences, Zhejiang University, Hangzhou, 310027, China.ORCID http://orcid.org/0009-0001-4187-4375
Jinyu ChenCollege of Life Sciences, Zhejiang University, Hangzhou, 310027, China.
Zhaoying ShiDepartment Of Chemical Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China.
Yonglong ChenDepartment Of Chemical Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China.ORCID http://orcid.org/0000-0002-4933-113X
Yong WangCollege of Life Sciences, Zhejiang University, Hangzhou, 310027, China. yongwang_isb@zju.edu.cn.ORCID http://orcid.org/0000-0001-9156-0377
Zhongmin LiuShenzhen Key Labortory of Biomolecular Assembling and Regulation, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China. liuzm@sustech.edu.cn.ORCID http://orcid.org/0000-0002-3280-3890

Funding

Guangdong Innovative and Entrepreneurial Research Team Program No. 2021ZT09Y104National Natural Science Foundation of China (National Science Foundation of China) No. 32000850National Natural Science Foundation of China (National Science Foundation of China) No. 32371275National Natural Science Foundation of China (National Science Foundation of China) No. 32371300Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation) No. LZ24C050003
6 · The paper itself

Abstract

Human multidrug resistance protein 5 (hMRP5) effluxes anticancer and antivirus drugs, driving multidrug resistance. To uncover the mechanism of hMRP5, we determine six distinct cryo-EM structures, revealing an autoinhibitory N-terminal peptide that must dissociate to permit subsequent substrate recruitment. Guided by these molecular insights, we design an inhibitory peptide that could block substrate entry into the transport pathway. We also identify a regulatory motif, comprising a positively charged cluster and hydrophobic patches, within the first nucleotide-binding domain that modulates hMRP5 localization by engaging with membranes. By integrating our structural, biochemical, computational, and cell biological findings, we propose a model for hMRP5 conformational cycling and localization. Overall, this work provides mechanistic understanding of hMRP5 function, while informing future selective hMRP5 inhibitor development. More broadly, this study advances our understanding of the structural dynamics and inhibition of ABC transporters.

Indexed as

Cryoelectron MicroscopyATP-Binding Cassette, Sub-Family C ProteinsATP-Binding Cassette TransportersBiological TransportHEK293 CellsHumansModels, MolecularPeptidesProtein ConformationABCC5 protein, humanATP-Binding Cassette, Sub-Family C ProteinsATP-Binding Cassette TransportersPeptides

Identifiers

PMID38844452
PMCPMC11156954

What OpenQuestion holds

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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.