Structural highlights
Function
YCFI_YEAST Cooperates for the ATP-dependent vacuolar transport of bilirubin and glutathione conjugates.[1] [2]
Publication Abstract from PubMed
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 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
- ↑ Petrovic S, Pascolo L, Gallo R, Cupelli F, Ostrow JD, Goffeau A, Tiribelli C, Bruschi CV. The products of YCF1 and YLL015w (BPT1) cooperate for the ATP-dependent vacuolar transport of unconjugated bilirubin in Saccharomyces cerevisiae. Yeast. 2000 Apr;16(6):561-71. PMID:10790694 doi:<561::AID-YEA551>3.0.CO;2-L http://dx.doi.org/10.1002/(SICI)1097-0061(200004)16:6<561::AID-YEA551>3.0.CO;2-L
- ↑ Li ZS, Szczypka M, Lu YP, Thiele DJ, Rea PA. The yeast cadmium factor protein (YCF1) is a vacuolar glutathione S-conjugate pump. J Biol Chem. 1996 Mar 15;271(11):6509-17. PMID:8626454
- ↑ Khandelwal NK, Millan CR, Zangari SI, Avila S, Williams D, Thaker TM, Tomasiak TM. The structural basis for regulation of the glutathione transporter Ycf1 by regulatory domain phosphorylation. Nat Commun. 2022 Mar 11;13(1):1278. doi: 10.1038/s41467-022-28811-w. PMID:35277487 doi:http://dx.doi.org/10.1038/s41467-022-28811-w
