{"doi":"10.1101/2022.12.22.521501","title":"Structural Basis of Prostaglandin Efflux by MRP4","abstract":"Abstract MRP4 is unique among the C family of ATP-binding cassette transporters for its role in translocating prostanoids, an important group of signaling molecules derived from unsaturated fatty acids. Using a reconstituted system, we report that a pair of prostaglandins (PGs) and the sulfonated-sterol DHEA-S preferentially enhance the ATPase activity of MRP4 over other previously proposed physiological substrates such as cyclic nucleotides or leukotrienes. We determined the cryo-EM structures of nanodisc embedded bovine MRP4 in (i) a nucleotide- and substrate-free state, (ii) in complex with PGE 1 , (iii) PGE 2 , and (iv) DHEA-S, and (v) a catalytically dead mutant E1202Q bound to ATP-Mg 2+ . The substrate-bound structures suggest unique features of the MRP4 binding site that distinguish its specificity for prostanoids from that of the related leukotriene transporter MRP1. The ATP-bound structure is in an outward-occluded conformation, revealing a novel state in the proposed alternate-access mechanism of MRP transport. Our study provides insights into the endogenous function of this versatile efflux transporter.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":302362,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":994356,"name":"Evan Green","orcid":"0000-0002-9758-4799","position":1,"is_corresponding":false},{"id":565938,"name":"Ruchika Bajaj","orcid":"0000-0002-9777-0364","position":2,"is_corresponding":false},{"id":289623,"name":"Ilan E. Chemmama","orcid":"0000-0002-5657-3516","position":3,"is_corresponding":false},{"id":771855,"name":"Giselle M. Knudsen","orcid":"0000-0001-5570-8493","position":4,"is_corresponding":false},{"id":108109,"name":"Meghna Gupta","orcid":"0000-0002-7432-3211","position":5,"is_corresponding":false},{"id":91660,"name":"Andrej Săli","orcid":"0000-0003-0435-6197","position":6,"is_corresponding":false},{"id":98188,"name":"Yifan Cheng","orcid":"0000-0001-9535-0369","position":7,"is_corresponding":false},{"id":288757,"name":"Charles S. Craik","orcid":"0000-0001-7704-9185","position":8,"is_corresponding":false},{"id":329570,"name":"Deanna L. Kroetz","orcid":"0000-0001-5997-270X","position":9,"is_corresponding":false},{"id":103698,"name":"Robert M. Stroud","orcid":"0000-0003-2083-5665","position":10,"is_corresponding":false},{"id":108110,"name":"Sergei Pourmal","orcid":"0000-0002-7537-6016","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T00:32:16.279991Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}