Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA.
Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3737-41. doi: 10.1073/pnas.1200255109. Epub 2012 Feb 21.
Multimeric AAA ATPases represent a structurally homologous yet functionally diverse family of proteins. The essential and highly abundant hexameric AAA ATPase p97 is perhaps the best studied AAA protein, playing an essential role in various important cellular activities. During ATP-hydrolysis process, p97 undergoes dramatic conformational changes, and these changes are initiated in the C-terminal ATPase domain and transmitted across the entire length of the molecule to the N-terminal effector domain. However, the detailed mechanism of the motion transmission remains unclear. Here, we report an interprotomer motion-transmission mechanism to explain this process: The nucleotide-dependent motion transmission between the two ATPase domains of one protomer is mediated by its neighboring protomer. This finding reveals a strict requirement for interprotomer coordination of p97 during the motion-transmission process and may shed light on studies of other AAA ATPases.
多聚体 AAA ATP 酶代表了一个结构同源但功能多样的蛋白质家族。六聚体 AAA ATP 酶 p97 是研究最为深入的 AAA 蛋白之一，在各种重要的细胞活动中发挥着至关重要的作用。在 ATP 水解过程中，p97 经历剧烈的构象变化，这些变化始于 C 端 ATP 酶结构域，并通过整个分子传递到 N 端效应结构域。然而，运动传递的详细机制尚不清楚。在这里，我们报告了一种蛋白间运动传递机制来解释这一过程：一个蛋白的两个 ATP 酶结构域之间的核苷酸依赖性运动传递是由其相邻蛋白介导的。这一发现揭示了 p97 在运动传递过程中对蛋白间协调的严格要求，这可能对其他 AAA ATP 酶的研究提供启示。
