Science：打开丙肝病毒DNA链的酶机制
生物谷：研究人员确定了一个对丙肝病毒DNA复制至关重要的酶的机制。这个名为NS3的酶是新的乙肝治疗法的靶标，它的作用是打开DNA和RNA使其得以复制。Sua Myong和同事用单分子光谱学方法观察了NS3沿乙肝病毒DNA双螺旋的“蠕动”。这个酶每步打开3个DNA碱基对(碱基对是DNA双股上对应的由氢键连接的核苷酸)。但是，在碱基对打开之前，还有隐藏的步骤。这个酶先是一、二大步，然后一个小步爬上碱基对，直到张力足够大从而导致解卷和3个碱基对看起来是同时的开链。
英文原文链接：
http://www.sciencedaily.com/releases/2007/07/070726142007.htm
Using single-molecule fluorescence analysis, Institute for Genomic Biology professor Sua Myong and physics professor Taekjip Ha led a team that discovered the mechanism by which the hepatitis C helicase unwinds DNA and RNA for replication. Ha is also affiliated with the Institute for Genomic Biology and the Howard Hughes Medical Center. (Credit: L. Brian Stauffer, U. of I. News Bureau)
原始出处:
Science 27 July 2007:
Vol. 317. no. 5837, pp. 513 - 516
DOI: 10.1126/science.1144130
Spring-Loaded Mechanism of DNA Unwinding by Hepatitis C Virus NS3 Helicase
Sua Myong,1,2* Michael M. Bruno,3,4 Anna M. Pyle,3,4 Taekjip Ha1,2,4
NS3, an essential helicase for replication of hepatitis C virus, is a model enzyme for investigating helicase function. Using single-molecule fluorescence analysis, we showed that NS3 unwinds DNA in discrete steps of about three base pairs (bp). Dwell time analysis indicated that about three hidden steps are required before a 3-bp step is taken. Taking into account the available structural data, we propose a spring-loaded mechanism in which several steps of one nucleotide per adenosine triphosphate molecule accumulate tension on the protein-DNA complex, which is relieved periodically via a burst of 3-bp unwinding. NS3 appears to shelter the displaced strand during unwinding, and, upon encountering a barrier or after unwinding >18 bp, it snaps or slips backward rapidly and repeats unwinding many times in succession. Such repetitive unwinding behavior over a short stretch of duplex may help to keep secondary structures resolved during viral genome replication.
1 Physics Department, University of Illinois, 1110 West Green Street, Urbana, IL 61801, USA.
2 Institute for Genomic Biology, University of Illinois, 1206 West Gregory Drive, Urbana, IL 61801, USA.
3 Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, Room 334A, Bass Building, New Haven, CT 06511, USA.
4 Howard Hughes Medical Institute.
* To whom correspondence should be addressed. E-mail: smyong@uiuc.edu
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