Disorder-order folding transitions underlie catalysis in the helicase motor of SecA
Disorder-order folding transitions underlie catalysis in the helicase motor of SecA
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DOI：
10.1038/nsmb1108
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发表时间：
2006-07-01
影响因子：
16.8
通讯作者：
Kalodimos, Charalampos G.
中科院分区：
文献类型：
--
作者：
Keramisanou, Dimitra;Biris, Nikolaos;Kalodimos, Charalampos G.
SECA是一种类似解旋酶的马达，它将ATP的水解与胞外蛋白底物的转位结合在一起。正如大多数解旋酶一样，这一过程被认为是通过核苷酸调节的运动域的刚体运动而发生的。核磁共振、热力学和生化数据表明，SecA使用了一种新的机制，即核苷酸裂解两侧的保守区在功能催化状态之间切换时经历无序-有序转变的循环。这些转换是由位于解旋酶基序上的关键的‘精氨酸手指’残基介导的域间相互作用来调节的。此外，我们发现核苷酸裂解与前蛋白底物结合域和调节的膜插入C结构域进行变构通信，从而允许ATPase循环与易位活性的耦合。与配体结合有关的内在可塑性和功能无序-有序折叠转变似乎提供了对催化激活过程的精确控制和变构机制的简单调节。
SecA is a helicase-like motor that couples ATP hydrolysis with the translocation of extracytoplasmic protein substrates. As in most helicases, this process is thought to occur through nucleotide-regulated rigid-body movement of the motor domains. NMR, thermodynamic and biochemical data show that SecA uses a novel mechanism wherein conserved regions lining the nucleotide cleft undergo cycles of disorder-order transitions while switching among functional catalytic states. The transitions are regulated by interdomain interactions mediated by crucial 'arginine finger' residues located on helicase motifs. Furthermore, we show that the nucleotide cleft allosterically communicates with the preprotein substrate - binding domain and the regulatory, membrane-inserting C domain, thereby allowing for the coupling of the ATPase cycle to the translocation activity. The intrinsic plasticity and functional disorder-order folding transitions coupled to ligand binding seem to provide a precise control of the catalytic activation process and simple regulation of allosteric mechanisms.