Department of Molecular Physiology and Biological Physics, University of Virginia, 480 Ray C. Hunt Drive, P.O. Box 800886, Charlottesville, VA 22908-0886, U.S.A.
Essays Biochem. 2011 Sep 7;50(1):63-83. doi: 10.1042/bse0500063.
ABC (ATP-binding cassette) transporters are arguably the most important family of ATP-driven transporters in biology. Despite considerable effort and advances in determining the structures and physiology of these transporters, their fundamental molecular mechanisms remain elusive and highly controversial. How does ATP hydrolysis by ABC transporters drive their transport function? Part of the problem in answering this question appears to be a perceived need to formulate a universal mechanism. Although it has been generally hoped and assumed that the whole superfamily of ABC transporters would exhibit similar conserved mechanisms, this is proving not to be the case. Structural considerations alone suggest that there are three overall types of coupling mechanisms related to ABC exporters, small ABC importers and large ABC importers. Biochemical and biophysical characterization leads us to the conclusion that, even within these three classes, the catalytic and transport mechanisms are not fully conserved, but continue to evolve. ABC transporters also exhibit unusual characteristics not observed in other primary transporters, such as uncoupled basal ATPase activity, that severely complicate mechanistic studies by established methods. In this chapter, I review these issues as related to ABC exporters in particular. A consensus view has emerged that ABC exporters follow alternating-access switch transport mechanisms. However, some biochemical data suggest that alternating catalytic site transport mechanisms are more appropriate for fully symmetrical ABC exporters. Heterodimeric and asymmetrical ABC exporters appear to conform to simple alternating-access-type mechanisms.
ABC（ATP 结合盒）转运蛋白可说是生物学中最重要的一类 ATP 驱动转运蛋白。尽管在确定这些转运蛋白的结构和生理学方面付出了相当大的努力和取得了进展，但它们的基本分子机制仍然难以捉摸且极具争议。ABC 转运蛋白如何通过 ATP 水解来驱动其转运功能？回答这个问题的部分问题似乎是需要制定一个通用机制。尽管人们普遍希望并假定整个 ABC 转运蛋白超家族将表现出类似的保守机制，但事实证明并非如此。仅结构上的考虑就表明，与 ABC 外排泵、小 ABC 输入泵和大 ABC 输入泵相关的耦合机制有三种总体类型。生化和生物物理特性表明，即使在这三类中，催化和转运机制也没有完全保守，而是继续进化。ABC 转运蛋白还表现出其他原发性转运蛋白所没有的不寻常特征，例如无偶联基础 ATP 酶活性，这使得通过既定方法进行的机制研究变得非常复杂。在这一章中，我特别回顾了这些与 ABC 外排泵有关的问题。已经出现了一种共识观点，即 ABC 外排泵遵循交替访问开关转运机制。然而，一些生化数据表明，交替催化位点转运机制更适合完全对称的 ABC 外排泵。异源二聚体和不对称 ABC 外排泵似乎符合简单的交替访问型机制。
