Nikles Daphne, Tampé Robert
Institute of Biochemistry, Biocenter, Johann Wolfgang Goethe-University, Max-von-Laue-Str. 9, 60348 Frankfurt am Main, Germany.
J Bioenerg Biomembr. 2007 Dec;39(5-6):489-97. doi: 10.1007/s10863-007-9120-z.
ATP binding cassette (ABC) transporters comprise an extended protein family involved in the transport of a broad spectrum of solutes across membranes. They consist of a common architecture including two ATP-binding domains converting chemical energy into conformational changes and two transmembrane domains facilitating transport via alternating access. This review focuses on the biogenesis, and more precisely, on the degradation of mammalian ABC transporters in the endoplasmic reticulum (ER). We enlighten the ER-associated degradation pathway in the context of misfolded, misassembled or tightly regulated ABC transporters with a closer view on the cystic fibrosis transmembrane conductance regulator (CFTR) and the transporter associated with antigen processing (TAP), which plays an essential role in the adaptive immunity. Three rather different scenarios affecting the stability and degradation of ABC transporters are discussed: (1) misfolded domains caused by a lack of proper intra- and intermolecular contacts within the ABC transporters, (2) deficient assembly with auxiliary factors, and (3) arrest and accumulation of an intermediate or 'dead-end' state in the transport cycle, which is prone to be recognized by the ER-associated degradation machinery.
ATP结合盒（ABC）转运蛋白构成了一个庞大的蛋白质家族，参与多种溶质跨膜运输。它们具有共同的结构，包括两个将化学能转化为构象变化的ATP结合结构域，以及两个通过交替通路促进运输的跨膜结构域。本综述聚焦于哺乳动物ABC转运蛋白在内质网（ER）中的生物合成，更确切地说是其降解过程。我们在错误折叠、组装错误或受到严格调控的ABC转运蛋白的背景下，阐述内质网相关降解途径，重点关注囊性纤维化跨膜传导调节因子（CFTR）和抗原加工相关转运蛋白（TAP），后者在适应性免疫中起关键作用。本文讨论了影响ABC转运蛋白稳定性和降解的三种截然不同的情况：（1）ABC转运蛋白内分子内和分子间缺乏适当接触导致结构域错误折叠；（2）与辅助因子组装不足；（3）运输循环中中间体或“终末”状态的停滞和积累，这种状态易于被内质网相关降解机制识别。
