Nanyang Technological University, School of Biological Sciences, 60 Nanyang Drive, 637551, Singapore.
Nanyang Technological University, School of Biological Sciences, 60 Nanyang Drive, 637551, Singapore.
Prog Biophys Mol Biol. 2019 May;143:67-77. doi: 10.1016/j.pbiomolbio.2018.08.008. Epub 2018 Aug 29.
Dengue- (DENV) and Zika viruses (ZIKV) rely on their non-structural protein 5 (NS5) including a methyl-transferase (MTase) and a RNA-dependent RNA polymerase (RdRp) for capping and synthesis of the viral RNA, and the non-structural protein 3 (NS3) with its protease and helicase domain for polyprotein possessing, unwinding dsRNA proceeding replication, and NTPase/RTPase activities. Accumulation of data for DENV- and ZIKV NS3 and NS5 in solution during recent years provides information about their overall shape, substrate-induced alterations, oligomeric forms and flexibility, with the latter being essential for domain-domain crosstalk. The importance and differences of the linker regions that connect the two domains of NS3 or NS5 are highlighted in particular with respect to the different DENV serotypes (DENV-1 to -4) as well as to the sequence diversities between the DENV and ZIKV proteins. Novel mutants of the French Polynesia ZIKV NS3 linker presented, identify critical residues in protein stability and enzymatic activity.
登革热病毒（DENV）和 Zika 病毒（ZIKV）依赖其非结构蛋白 5（NS5），包括一个甲基转移酶（MTase）和一个 RNA 依赖性 RNA 聚合酶（RdRp），用于对病毒 RNA 进行加帽和合成，以及非结构蛋白 3（NS3）及其蛋白酶和解旋酶结构域，用于具有多蛋白的 RNA 解旋、dsRNA 复制以及 NTPase/RTPase 活性。近年来，有关 DENV 和 ZIKV NS3 和 NS5 在溶液中的数据积累，提供了有关其整体形状、底物诱导变化、寡聚形式和灵活性的信息，后者对于域间相互作用至关重要。连接 NS3 或 NS5 的两个结构域的连接区的重要性和差异，特别是对于不同的 DENV 血清型（DENV-1 至 DENV-4）以及 DENV 和 ZIKV 蛋白之间的序列多样性，都得到了强调。来自法属波利尼西亚 Zika 病毒 NS3 连接区的新型突变体表明，该蛋白稳定性和酶活性的关键残基。
