Balasco Nicole, Barone Daniela, Sandomenico Annamaria, Ruggiero Alessia, Doti Nunzianna, Berisio Rita, Ruvo Menotti, Vitagliano Luigi
Institute of Biostructures and Bioimaging, CNR, Naples, Italy.
Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche, Università della Campania "Luigi Vanvitelli", Caserta 81100, Italy.
Curr Med Chem. 2017 Nov 24;24(36):4081-4101. doi: 10.2174/0929867324666170508105544.
HCV-linked pathologies represent worldwide health threats. Over the years, an enormous number of independent studies have been devoted to the understanding of the molecular bases of HCV infection. A significant amount of these investigations has been focused on the structural characterization of the virus proteins with the aim of developing structure-based innovative therapeutic approaches. An analysis of the current Protein Data Bank content unravels that the structural biology of the virus has hitherto covered a large fraction of the HCV proteins (75%).
The present review recapitulates the state-of-the-art of structural characterizations of HCV individual proteins with a specific focus on their structural versatility/flexibility.
This survey indicates there is accumulating evidence that structural flexibility is a common feature among HCV proteins. This versatility can be detected at different structural level i.e. occurrence of alternative oligomeric states and/or of local and global flexibility. Somewhat surprisingly, some disordered or highly flexible regions of HCV proteins, such as the core and the antigenic fragment 412-423 of E2, present highly conserved sequences among the virus genotypes. The overall versatility of HCV proteins plays an important role in host protein recognition, drug resistance mechanisms, and virus escape from the host immunogenic system. Of particular relevance is the emerging idea that HCV uses local structural flexibility as an alternative tool to sequence variability to evade the immune response of the host organism.
We believe that concepts emerged from this survey will be important for the development of anti-HCV vaccines that are eagerly needed.
丙型肝炎病毒（HCV）相关疾病是全球健康威胁。多年来，大量独立研究致力于了解HCV感染的分子基础。这些研究中有相当一部分聚焦于病毒蛋白的结构表征，目的是开发基于结构的创新治疗方法。对当前蛋白质数据库内容的分析表明，迄今为止，病毒的结构生物学已涵盖了大部分HCV蛋白（75%）。
本综述概述了HCV单个蛋白结构表征的最新进展，特别关注其结构的多功能性/灵活性。
这项调查表明，越来越多的证据表明结构灵活性是HCV蛋白的共同特征。这种多功能性可以在不同结构水平上检测到，即出现替代寡聚状态和/或局部和全局灵活性。有点令人惊讶的是，HCV蛋白的一些无序或高度灵活的区域，如核心蛋白和E2的抗原片段412 - 423，在病毒基因型中具有高度保守的序列。HCV蛋白的整体多功能性在宿主蛋白识别、耐药机制以及病毒逃避宿主免疫原系统中起着重要作用。特别相关的是，新出现的观点认为HCV利用局部结构灵活性作为序列变异性的替代工具来逃避宿主生物体的免疫反应。
我们认为，本次调查中出现的概念对于迫切需要的抗HCV疫苗的开发将具有重要意义。
