Cashikar Anil G, Schirmer Eric C, Hattendorf Douglas A, Glover John R, Ramakrishnan Melarkode S, Ware Danielle M, Lindquist Susan L
Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA.
Mol Cell. 2002 Apr;9(4):751-60. doi: 10.1016/s1097-2765(02)00499-9.
AAA proteins remodel other proteins to affect a multitude of biological processes. Their power to remodel substrates must lie in their capacity to couple substrate binding to conformational changes via cycles of nucleotide binding and hydrolysis, but these relationships have not yet been deciphered for any member. We report that when one AAA protein, Hsp104, engages polypeptide at the C-terminal peptide-binding region, the ATPase cycle of the C-terminal nucleotide-binding domain (NBD2) drives a conformational change in the middle region. This, in turn, drives ATP hydrolysis in the N-terminal ATPase domain (NBD1). This interdomain communication pathway can be blocked by mutation in the middle region or bypassed by antibodies that bind there, demonstrating the crucial role this region plays in transducing signals from one end of the molecule to the other.
AAA蛋白通过重塑其他蛋白质来影响众多生物过程。它们重塑底物的能力必定源于其通过核苷酸结合和水解循环将底物结合与构象变化相耦合的能力，但对于任何一个成员而言，这些关系尚未被破解。我们报告称，当一种AAA蛋白Hsp104在C端肽结合区域与多肽结合时，C端核苷酸结合结构域（NBD2）的ATP酶循环驱动中间区域发生构象变化。反过来，这又驱动N端ATP酶结构域（NBD1）中的ATP水解。这种结构域间的通讯途径可被中间区域的突变阻断，或被结合在该区域的抗体绕过，这表明该区域在将信号从分子一端传递到另一端中发挥着关键作用。
