7m68 | pdb_00007m68
E1435Q Ycf1 mutant in inward-facing narrow conformation
Structural highlights
FunctionYCFI_YEAST Cooperates for the ATP-dependent vacuolar transport of bilirubin and glutathione conjugates.[1] [2] Publication Abstract from PubMedYeast 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 A and 4.0 A 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 structures and are related by rigid body movements of the NBD1/R-domain complex. Biochemical data further show R-domain phosphorylation reorganizes the Ycf1 architecture and is required for maximal ATPase activity. Together, we provide insights into how R-domains control ABCC transporter activity. The structural basis for regulation of the glutathione transporter Ycf1 by regulatory domain phosphorylation.,Khandelwal NK, Millan CR, Zangari SI, Avila S, Williams D, Thaker TM, Tomasiak TM Nat Commun. 2022 Mar 11;13(1):1278. doi: 10.1038/s41467-022-28811-w. PMID:35277487[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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