{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Khandelwal NK"],"funding":["U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences","NIAID NIH HHS","NIH HHS","Division of Intramural Research, National Institute of Allergy and Infectious Diseases","NIGMS NIH HHS"],"pagination":["1278"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8917219"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(1)"],"pubmed_abstract":["Yeast Cadmium Factor 1 (Ycf1) sequesters heavy metals and glutathione into the vacuole to counter cell stress. Ycf1 belongs to the ATP binding cassette C-subfamily (ABCC) of transporters, many of which are regulated by phosphorylation on intrinsically-disordered domains. The regulatory mechanism of phosphorylation is still poorly understood. Here, we report two cryo-EM structures of Ycf1 at 3.4 Å and 4.0 Å resolution in inward-facing open conformations that capture previously unobserved ordered states of the intrinsically disordered regulatory domain (R-domain). R-domain phosphorylation is clearly evident and induces a topology promoting electrostatic and hydrophobic interactions with Nucleotide Binding Domain 1 (NBD1) and the Lasso motif. These interactions stay constant between the struc"],"journal":["Nature communications"],"pubmed_title":["The structural basis for regulation of the glutathione transporter Ycf1 by regulatory domain phosphorylation."],"pmcid":["PMC8917219"],"funding_grant_id":["R01AI156270","R00GM11424","U24 GM129547","R00 GM114245","R01 AI156270","S10 OD011981"],"pubmed_authors":["Millan CR","Zangari SI","Tomasiak TM","Avila S","Williams D","Thaker TM","Khandelwal NK"],"additional_accession":[]},"is_claimable":false,"name":"The structural basis for regulation of the glutathione transporter Ycf1 by regulatory domain phosphorylation.","description":"Yeast Cadmium Factor 1 (Ycf1) sequesters heavy metals and glutathione into the vacuole to counter cell stress. Ycf1 belongs to the ATP binding cassette C-subfamily (ABCC) of transporters, many of which are regulated by phosphorylation on intrinsically-disordered domains. The regulatory mechanism of phosphorylation is still poorly understood. Here, we report two cryo-EM structures of Ycf1 at 3.4 Å and 4.0 Å resolution in inward-facing open conformations that capture previously unobserved ordered states of the intrinsically disordered regulatory domain (R-domain). R-domain phosphorylation is clearly evident and induces a topology promoting electrostatic and hydrophobic interactions with Nucleotide Binding Domain 1 (NBD1) and the Lasso motif. These interactions stay constant between the struc","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2026-05-10T01:38:23.699Z","creation":"2025-02-19T01:11:56.178Z"},"accession":"S-EPMC8917219","cross_references":{"pubmed":["35277487"],"doi":["10.1038/s41467-022-28811-w"]}}