Domain 2 of nonstructural protein 5A (NS5A) of hepatitis C virus is natively unfolded
Domain 2 of nonstructural protein 5A (NS5A) of hepatitis C virus is natively unfolded
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DOI：
10.1021/bi700776e
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发表时间：
2007-10-16
期刊：
影响因子：
2.9
通讯作者：
Yoon, Ho Sup
中科院分区：
文献类型：
--
作者：
Liang, Yu;Ye, Hong;Yoon, Ho Sup
丙型肝炎病毒（HCV）非结构蛋白5A（NS 5A）在病毒复制、干扰素抗性和细胞凋亡的调节中起重要作用。HCV NS 5A包含三个结构域。最近的结构域1的结构已被确定，揭示了一个新的锌结合基序和二硫键的结构支架。目前，结构域2和3的结构仍不确定。HCV NS 5A的结构域2（NS 5A-D2）对NS 5A的功能非常重要，并参与与其自身的NS 5 B和PKR（细胞干扰素诱导的丝氨酸/苏氨酸特异性蛋白激酶）的分子相互作用。在这项研究中，我们进行了结构域2多核核磁共振（NMR）光谱的结构分析。对骨架H-1、C-13和N-15共振、（3）J（HN alpha）偶联常数和3D NOE数据的分析表明NS 5A-D2缺乏二级结构元件，并揭示了未折叠蛋白质的特征。核磁共振弛豫参数证实了缺乏刚性结构的域。NS 5A-D2的有序构象的缺乏和高度动态行为的观察可以提供其生理功能的潜在分子基础，以允许NS 5A-D2与各种生物学伴侣相互作用。
Nonstructural protein 5A protein (NS5A) of hepatitis C virus (HCV) plays an important role in the regulation of viral replication, interferon resistance, and apoptosis. HCV NS5A comprises three domains. Recently the structure of domain 1 has been determined, revealing a structural scaffold with a novel zinc-binding motif and a disulfide bond. At present, the structures of domains 2 and 3 remain undefined. Domain 2 of HCV NS5A (NS5A-D2) is important for functions of NS5A and involved in molecular interactions with its own NS5B and PKR, a cellular interferon-inducible serine/threonine specific protein kinase. In this study we performed structural analysis of domain 2 by multinuclear nuclear magnetic resonance (NMR) spectroscopy. The analysis of the backbone H-1, C-13, and N-15 resonances, (3)J(HN alpha) coupling constants and 3D NOE data indicates that NS5A-D2 lacks secondary structural elements and reveals characteristics of unfolded proteins. NMR relaxation parameters confirmed the lack of rigid structure in the domain. The absence of an ordered conformation and the observation of a highly dynamic behavior of NS5A-D2 may provide an underlying molecular basis on its physiological function to allow NS5A-D2 to interact with a variety of biological partners.