Sousa Rui, Liao Hsien-Shun, Cuéllar Jorge, Jin Suping, Valpuesta José M, Jin Albert J, Lafer Eileen M
Department of Biochemistry and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA.
Nat Struct Mol Biol. 2016 Sep;23(9):821-9. doi: 10.1038/nsmb.3272. Epub 2016 Aug 1.
Hsp70s use ATP hydrolysis to disrupt protein-protein associations and to move macromolecules. One example is the Hsc70- mediated disassembly of the clathrin coats that form on vesicles during endocytosis. Here, we exploited the exceptional features of these coats to test three models-Brownian ratchet, power-stroke and entropic pulling-proposed to explain how Hsp70s transform their substrates. Our data rule out the ratchet and power-stroke models and instead support a collision-pressure mechanism whereby collisions between clathrin-coat walls and Hsc70s drive coats apart. Collision pressure is the complement to the pulling force described in the entropic pulling model. We also found that self-association augments collision pressure, thereby allowing disassembly of clathrin lattices that have been predicted to be resistant to disassembly. These results illuminate how Hsp70s generate the forces that transform their substrates.
热休克蛋白70（Hsp70s）利用ATP水解来破坏蛋白质-蛋白质相互作用并移动大分子。一个例子是Hsc70介导的网格蛋白衣被的拆卸，网格蛋白衣被在内吞作用期间在囊泡上形成。在这里，我们利用这些衣被的特殊特性来测试三种模型——布朗棘轮模型、动力冲程模型和熵拉动模型，这些模型被提出来解释Hsp70s如何转化其底物。我们的数据排除了棘轮模型和动力冲程模型，转而支持一种碰撞压力机制，即网格蛋白衣被壁与Hsc70s之间的碰撞驱动衣被分开。碰撞压力是熵拉动模型中描述的拉力的补充。我们还发现自我缔合增强了碰撞压力，从而使得预计对拆卸有抗性的网格蛋白晶格能够被拆卸。这些结果阐明了Hsp70s如何产生转化其底物的力。
