Department of Chemistry, University of California, Berkeley, California 94720, USA.
Protein Sci. 2012 May;21(5):606-24. doi: 10.1002/pro.2052. Epub 2012 Mar 30.
Energy-consuming nanomachines catalyze the directed movement of biopolymers in the cell. They are found both dissolved in the aqueous cytosol as well as embedded in lipid bilayers. Inquiries into the molecular mechanism of nanomachine-catalyzed biopolymer transport have revealed that these machines are equipped with molecular parts, including adjustable clamps, levers, and adaptors, which interact favorably with substrate polypeptides. Biological nanomachines that catalyze protein transport, known as translocases, often require that their substrate proteins unfold before translocation. An unstructured protein chain is likely entropically challenging to bind, push, or pull in a directional manner, especially in a way that produces an unfolding force. A number of ingenious solutions to this problem are now evident in the anthrax toxin system, a model used to study protein translocation. Here we highlight molecular ratchets and current research on anthrax toxin translocation. A picture is emerging of proton-gradient-driven anthrax toxin translocation, and its associated ratchet mechanism likely applies broadly to other systems. We suggest a cyclical thermodynamic order-to-disorder mechanism (akin to a heat-engine cycle) is central to underlying protein translocation: peptide substrates nonspecifically bind to molecular clamps, which possess adjustable affinities; polypeptide substrates compress into helical structures; these clamps undergo proton-gated switching; and the substrate subsequently expands regaining its unfolded state conformational entropy upon translocation.
耗能纳米机器可催化生物聚合物在细胞中的定向运动。它们既存在于溶解在水相细胞质中的溶液中，也存在于嵌入脂质双层的溶液中。对纳米机器催化的生物聚合物运输的分子机制的研究表明，这些机器配备了分子部件，包括可调节的夹具、杠杆和接头，它们与底物多肽相互作用良好。催化蛋白质运输的生物纳米机器，称为转位酶，通常要求其底物蛋白质在易位前展开。无结构的蛋白质链可能在热力学上难以结合、推动或拉动以定向方式，特别是在产生展开力的方式上。目前在炭疽毒素系统中已经明显出现了许多解决此问题的巧妙方法，炭疽毒素系统是用于研究蛋白质易位的模型。在这里，我们重点介绍分子棘轮和炭疽毒素易位的当前研究。一幅质子梯度驱动的炭疽毒素易位及其相关棘轮机制的图片正在浮现，其相关的棘轮机制可能广泛适用于其他系统。我们提出了一种循环热力学有序到无序的机制（类似于热机循环），是潜在的蛋白质易位的基础：肽底物非特异性地结合到具有可调节亲和力的分子夹具上；多肽底物压缩成螺旋结构；这些夹具经历质子门控切换；随后，底物在易位后扩展，重新获得其展开状态的构象熵。
