A Brownian motor mechanism of translocation and strand separation by hepatitis C virus helicase
A Brownian motor mechanism of translocation and strand separation by hepatitis C virus helicase
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DOI：
10.1038/nsmb920
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发表时间：
2005-05-01
影响因子：
16.8
通讯作者：
Patel, SS
中科院分区：
文献类型：
--
作者：
Levin, MK;Gurjar, M;Patel, SS
解旋酶利用ATP水解的能量并通过改变核酸结合位点的构象沿其核酸底物进行转运。我们的目标是表征丙型肝炎病毒（HCV）解旋酶在atp酶周期的不同阶段的构象变化，并确定它们如何导致易位。我们已经报道了ATP结合降低了HCV解旋酶对核酸的亲和力。现在我们确定了atp酶周期中负责易位和解绕的阶段。我们发现，在没有ATP的情况下，解旋酶与DNA结合时发生了快速的定向运动，导致几个碱基对的打开。我们提出HCV解旋酶易位为布朗马达，具有简单的二冲程循环。定向运动步骤是由单链DNA结合能量推动的，而ATP结合允许短暂的随机运动，为下一个循环做准备。
Helicases translocate along their nucleic acid substrates using the energy of ATP hydrolysis and by changing conformations of their nucleic acid - binding sites. Our goal is to characterize the conformational changes of hepatitis C virus (HCV) helicase at different stages of ATPase cycle and to determine how they lead to translocation. We have reported that ATP binding reduces HCV helicase affinity for nucleic acid. Now we identify the stage of the ATPase cycle responsible for translocation and unwinding. We show that a rapid directional movement occurs upon helicase binding to DNA in the absence of ATP, resulting in opening of several base pairs. We propose that HCV helicase translocates as a Brownian motor with a simple two-stroke cycle. The directional movement step is fueled by single-stranded DNA binding energy while ATP binding allows for a brief period of random movement that prepares the helicase for the next cycle.