Reissmann Stefanie, Parnot Charles, Booth Christopher R, Chiu Wah, Frydman Judith
Department of Biological Sciences and BioX Program, Stanford University, Stanford, California 94305, USA.
Nat Struct Mol Biol. 2007 May;14(5):432-40. doi: 10.1038/nsmb1236. Epub 2007 Apr 29.
Chaperonins are allosteric double-ring ATPases that mediate cellular protein folding. ATP binding and hydrolysis control opening and closing of the central chaperonin chamber, which transiently provides a protected environment for protein folding. During evolution, two strategies to close the chaperonin chamber have emerged. Archaeal and eukaryotic group II chaperonins contain a built-in lid, whereas bacterial chaperonins use a ring-shaped cofactor as a detachable lid. Here we show that the built-in lid is an allosteric regulator of group II chaperonins, which helps synchronize the subunits within one ring and, to our surprise, also influences inter-ring communication. The lid is dispensable for substrate binding and ATP hydrolysis, but is required for productive substrate folding. These regulatory functions of the lid may serve to allow the symmetrical chaperonins to function as 'two-stroke' motors and may also provide a timer for substrate encapsulation within the closed chamber.
伴侣蛋白是介导细胞内蛋白质折叠的变构双环ATP酶。ATP的结合和水解控制着伴侣蛋白中央腔的打开和关闭，该腔为蛋白质折叠瞬时提供了一个受保护的环境。在进化过程中，出现了两种关闭伴侣蛋白腔的策略。古菌和真核生物的II型伴侣蛋白含有一个内置盖子，而细菌伴侣蛋白则使用一个环形辅因子作为可拆卸盖子。在这里，我们表明内置盖子是II型伴侣蛋白的变构调节剂，它有助于使一个环内的亚基同步，而且令我们惊讶的是，它还影响环间通讯。盖子对于底物结合和ATP水解是可有可无的，但对于底物的有效折叠是必需的。盖子的这些调节功能可能有助于使对称的伴侣蛋白作为“二冲程”马达发挥作用，也可能为底物在封闭腔内的包裹提供一个定时器。
