ArticleNature communications2024
Structural basis for the modulation of MRP2 activity by phosphorylation and drugs.
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 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Molecular basis of Arabidopsis ABCC2 in plant detoxification.Cell discovery · 2026Article
- Developing Potent Therapeutics for Liver Cancer Chemoresistance via an RNA Nanotech and Series-Circuit-Christmas-Bulb Mechanism Targeting ABC Transporters.Molecular pharmaceutics · 2026Review
- Transepithelial Transport of Caffeoylquinic Acids in Caco-2 Cells: Structure Dependence and Modulation by Dietary Flavonoids.Foods (Basel, Switzerland) · 2026Article
- Adenosine triphosphate-binding cassette transporters: key players in maintaining fetal health during pregnancy.Frontiers in endocrinology · 2026Review
- Recapitulating dengue virus infection with human pluripotent stem cell-derived liver organoids for antiviral screening.Nature communications · 2025Article
- X-Ray Irradiation Induces Oxidative Stress and Upregulates Intestinal Nrf2-Mrp2 Pathway, Leading to Decreased Intestinal Absorption of Valsartan.Pharmaceutics · 2025Article
- Structural basis for the transport and regulation mechanism of the multidrug resistance-associated protein 2.Nature communications · 2025Article
- Screening and evaluation of purines-degrading lactic acid bacteria isolated from traditional fermented foods in Yunnan Province and their uric acid-lowering effectsFrontiers in microbiology · 2025Article
- High serum unconjugated bilirubin levels following successful treatment of antiepileptic drug-induced bullosa epidermolysis: a case report and review of the literature.Frontiers in medicine · 2025Article
- Structure of a dimeric full-length ABC transporter.Nature communications · 2024Article
- Cryo-EM reveals a phosphorylated R-domain envelops the NBD1 catalytic domain in an ABC transporter.Life science alliance · 2024Article
- Structural basis for autoinhibition by the dephosphorylated regulatory domain of Ycf1.Nature communications · 2024Article
- Engineered liver-derived decellularized extracellular matrix-based three-dimensional tumor constructs for enhanced drug screening efficiency.Regenerative biomaterials · 2024Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multidrug resistance-associated protein 2 (MRP2/ABCC2) is a polyspecific efflux transporter of organic anions expressed in hepatocyte canalicular membranes. MRP2 dysfunction, in Dubin-Johnson syndrome or by off-target inhibition, for example by the uricosuric drug probenecid, elevates circulating bilirubin glucuronide and is a cause of jaundice. Here, we determine the cryo-EM structure of rat Mrp2 (rMrp2) in an autoinhibited state and in complex with probenecid. The autoinhibited state exhibits an unusual conformation for this class of transporter in which the regulatory domain is folded within the transmembrane domain cavity. In vitro phosphorylation, mass spectrometry and transport assays show that phosphorylation of the regulatory domain relieves this autoinhibition and enhances rMrp2 transport activity. The in vitro data is confirmed in human hepatocyte-like cells, in which inhibition of endogenous kinases also reduces human MRP2 transport activity. The drug-bound state reveals two probenecid binding sites that suggest a dynamic interplay with autoinhibition. Mapping of the Dubin-Johnson mutations onto the rodent structure indicates that many may interfere with the transition between conformational states.
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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.