Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Microbiol Mol Biol Rev. 2009 Dec;73(4):577-93. doi: 10.1128/MMBR.00020-09.
Members of the ATP-binding cassette (ABC) transporter superfamily exist in bacteria, fungi, plants, and animals and play key roles in the efflux of xenobiotic compounds, physiological substrates, and toxic intracellular metabolites. Based on sequence relatedness, mammalian ABC proteins have been divided into seven subfamilies, ABC subfamily A (ABCA) to ABCG. This review focuses on recent advances in our understanding of ABC transporters in the model organism Saccharomyces cerevisiae. We propose a revised unified nomenclature for the six yeast ABC subfamilies to reflect the current mammalian designations ABCA to ABCG. In addition, we specifically review the well-studied yeast ABCC subfamily (formerly designated the MRP/CFTR subfamily), which includes six members (Ycf1p, Bpt1p, Ybt1p/Bat1p, Nft1p, Vmr1p, and Yor1p). We focus on Ycf1p, the best-characterized yeast ABCC transporter. Ycf1p is located in the vacuolar membrane in yeast and functions in a manner analogous to that of the human multidrug resistance-related protein (MRP1, also called ABCC1), mediating the transport of glutathione-conjugated toxic compounds. We review what is known about Ycf1p substrates, trafficking, processing, posttranslational modifications, regulation, and interactors. Finally, we discuss a powerful new yeast two-hybrid technology called integrated membrane yeast two-hybrid (iMYTH) technology, which was designed to identify interactors of membrane proteins. iMYTH technology has successfully identified novel interactors of Ycf1p and promises to be an invaluable tool in future efforts to comprehensively define the yeast ABC interactome.
ATP 结合盒（ABC）转运蛋白超家族成员存在于细菌、真菌、植物和动物中，在排出外源性化合物、生理底物和有毒细胞内代谢物方面发挥着关键作用。根据序列相关性，哺乳动物 ABC 蛋白已分为七个亚家族，即 ABC 亚家族 A（ABCA）至 ABCG。本综述重点介绍了我们对模式生物酿酒酵母中 ABC 转运蛋白的最新认识。我们提出了一个修订后的统一命名法，用于反映当前哺乳动物的 ABCA 至 ABCG 命名，用于六个酵母 ABC 亚家族。此外，我们特别回顾了研究较为深入的酵母 ABCC 亚家族（以前称为 MRP/CFTR 亚家族），该亚家族包括六个成员（Ycf1p、Bpt1p、Ybt1p/Bat1p、Nft1p、Vmr1p 和 Yor1p）。我们重点介绍了酵母 ABCC 转运蛋白中研究最为充分的 Ycf1p。Ycf1p 位于酵母的液泡膜中，其功能类似于人类多药耐药相关蛋白（MRP1，也称为 ABCC1），介导谷胱甘肽缀合的有毒化合物的转运。我们综述了已知的 Ycf1p 底物、运输、加工、翻译后修饰、调节和相互作用物。最后，我们讨论了一种称为整合膜酵母双杂交（iMYTH）的强大新型酵母双杂交技术，该技术旨在鉴定膜蛋白的相互作用物。iMYTH 技术已成功鉴定出 Ycf1p 的新相互作用物，有望成为未来全面定义酵母 ABC 相互作用组的宝贵工具。
