Defining a pathway of communication from the C-terminal peptide binding domain to the N-terminal ATPase domain in a AAA protein
Defining a pathway of communication from the C-terminal peptide binding domain to the N-terminal ATPase domain in a AAA protein
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DOI：
10.1016/s1097-2765(02)00499-9
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发表时间：
2002-04-01
期刊：
影响因子：
16
通讯作者：
Lindquist, SL
中科院分区：
文献类型：
--
作者：
Cashikar, AG;Schirmer, EC;Lindquist, SL
AAA蛋白重塑其他蛋白质以影响多种生物过程。它们改造底物的能力必须在于它们通过核苷酸结合和水解循环将底物结合与构象变化结合的能力，但这些关系尚未被任何成员破译。我们报道，当一个AAA蛋白Hsp104在c端肽结合区与多肽结合时，c端核苷酸结合域（NBD2）的atp酶循环驱动中间区域的构象变化。这反过来又驱动n端ATP酶结构域（NBD1）的ATP水解。这种区域间的通信途径可以被中间区域的突变阻断，也可以被结合在那里的抗体绕过，这表明该区域在将信号从分子的一端传导到另一端方面起着至关重要的作用。
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.