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-Structure paper
タイトル | The structural basis for regulation of the glutathione transporter Ycf1 by regulatory domain phosphorylation. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 1278, Year 2022 |
掲載日 | 2022年3月11日 |
著者 | Nitesh Kumar Khandelwal / Cinthia R Millan / Samantha I Zangari / Samantha Avila / Dewight Williams / Tarjani M Thaker / Thomas M Tomasiak / |
PubMed 要旨 | 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 ...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 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. |
リンク | Nat Commun / PubMed:35277487 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.42 - 4.04 Å |
構造データ | EMDB-23690, PDB-7m68: EMDB-23691, PDB-7m69: |
由来 |
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キーワード | MEMBRANE PROTEIN / ABC transporter |