ArticleNature communications2024
Transport mechanism of human bilirubin transporter ABCC2 tuned by the inter-module regulatory domain.
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 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Efficacy of glutamine supplementation in postoperative patients undergoing hepatic surgery: a systematic review and meta-analysis of randomized controlled trials.Clinics (Sao Paulo, Brazil) · 2026Article
- Molecular basis of Arabidopsis ABCC2 in plant detoxification.Cell discovery · 2026Article
- Functional implications of the conformational landscape of a multidrug transporter revealed by Zebrafish Abcb4 structures.Nature communications · 2026Article
- Developing Potent Therapeutics for Liver Cancer Chemoresistance via an RNA Nanotech and Series-Circuit-Christmas-Bulb Mechanism Targeting ABC Transporters.Molecular pharmaceutics · 2026Review
- Adenosine triphosphate-binding cassette transporters: key players in maintaining fetal health during pregnancy.Frontiers in endocrinology · 2026Review
- Structural insights into toxicant export mediated by ABCC2 in Arabidopsis thaliana.Nature communications · 2025Article
- Substrate recognition diversity and transport dynamics of ABCC1.Nature communications · 2025Article
- Nucleotide-dependent conformational changes direct peptide export by the transporter associated with antigen processing.Immunity · 2025Article
- A recurrent ABCC2 c.2439 + 5G > A variant disturbs mRNA splicing and causes Dubin-Johnson syndrome.BMC medical genomics · 2025Article
- Integrating Bulk and Single-Cell Transcriptomics with Machine Learning Reveals a Heme Metabolism-Based Panel for Lung Adenocarcinoma Chemotherapy Resistance.International journal of molecular sciences · 2025Article
- Structural basis for the transport and regulation mechanism of the multidrug resistance-associated protein 2.Nature communications · 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
- ATP-Binding Cassette and Solute Carrier Transporters: Understanding Their Mechanisms and Drug Modulation Through Structural and Modeling Approaches.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Cryo-EM reveals a phosphorylated R-domain envelops the NBD1 catalytic domain in an ABC transporter.Life science alliance · 2024Article
- Structural insight into binding site access and ligand recognition by human ABCB1.bioRxiv : the preprint server for biology · 2024Article
- Structural basis for autoinhibition by the dephosphorylated regulatory domain of Ycf1.Nature communications · 2024Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bilirubin is mainly generated from the breakdown of heme when red blood cells reach the end of their lifespan. Accumulation of bilirubin in human body usually leads to various disorders, including jaundice and liver disease. Bilirubin is conjugated in hepatocytes and excreted to bile duct via the ATP-binding cassette transporter ABCC2, dysfunction of which would lead to Dubin-Johnson syndrome. Here we determine the structures of ABCC2 in the apo, substrate-bound and ATP/ADP-bound forms using the cryo-electron microscopy, exhibiting a full transporter with a regulatory (R) domain inserted between the two half modules. Combined with substrate-stimulated ATPase and transport activity assays, structural analysis enables us to figure out transport cycle of ABCC2 with the R domain adopting various conformations. At the rest state, the R domain binding to the translocation cavity functions as an affinity filter that allows the substrates of high affinity to be transported in priority. Upon substrate binding, the R domain is expelled from the cavity and docks to the lateral of transmembrane domain following ATP hydrolysis. Our findings provide structural insights into a transport mechanism of ABC transporters finely tuned by the R domain.
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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.