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Unlike dengue virus, the conserved 14-23 residues in N-terminal region of Zika virus capsid is not involved in lipid interactions.
Biochimica et Biophysica Acta (BBA) - Biomembranes ( IF 3.4 ) Pub Date : 2020-08-09 , DOI: 10.1016/j.bbamem.2020.183440
Kumar Udit Saumya 1 , Deepak Kumar 1 , Prateek Kumar 1 , Rajanish Giri 1
Affiliation  

Zika virus capsid protein is involved in multiple essential steps of the viral life cycle. Many vital functionalities are attributed to the dynamic N- terminal domain of this protein, which is intrinsically disordered in ZIKV and among several flaviviruses too. Other than genome encapsulation, studies have shown interaction with host lipid droplets to be crucial for replication and maturation. In Dengue virus, the molecular basis of such interplay has been studied in detail, and residues within the capsid N-terminal disordered domain has been mapped. It revealed a new function of a conserved region in mediating capsid-lipid droplet association through a conformational transition. Therefore, in this study, we attempt to analyze the structural dynamics of Zika virus capsid's N- terminal domain and analyzed it through a reductionist approach by dividing the N-terminal domain into three truncated segments and studied them individually. Techniques such as Circular dichroism spectroscopy, Dynamic light scattering, Zeta potential and Molecular dynamic simulations were employed to identify the motif responsible for structural flexibility and ability to interact with membrane models. Our results confirm that the truncated segments 5–26 and 1–30 readily adopt an α-helical conformation in the presence of 2,2,2-trifluoro-ethanol, detergent and negatively charged phospholipids. However, in contrast to Dengue virus, we report the conserved residues 14–23 region to be unstructured and do not undergo a conformational switch in Zika virus. Thus, our study illustrates the possibility of conserved 14–23 region's non-involvement in ZIKV capsid-lipid droplet association, unlike DENV.



中文翻译:

与登革热病毒不同,寨卡病毒衣壳N端区域的保守14-23残基不参与脂质相互作用。

寨卡病毒衣壳蛋白参与病毒生命周期的多个基本步骤。许多重要功能归因于该蛋白的动态N末端结构域,该结构在ZIKV和几种黄病毒中也固有地紊乱。除基因组封装外,研究表明与宿主脂质小滴的相互作用对于复制和成熟至关重要。在登革热病毒中,已经详细研究了这种相互作用的分子基础,并且已经绘制了衣壳N端无序域内的残基。它揭示了保守区域在通过构象转变介导衣壳-脂质液滴缔合中的新功能。因此,在这项研究中,我们试图分析寨卡病毒衣壳的结构动力学。s的N末端结构域,并通过还原论方法进行分析,将N末端结构域分为三个截短的片段,并分别进行研究。采用圆二色谱,动态光散射,Zeta电位和分子动力学模拟等技术来鉴定负责结构柔韧性和与膜模型相互作用的基序。我们的结果证实,截短的5–26和1–30段容易采用在2,2,2-三氟乙醇,去污剂和带负电荷的磷脂存在下的α-螺旋构象。但是,与登革热病毒相反,我们报告了寨卡病毒中保守的14-23残基区域是非结构化的,并且未经历构象转换。因此,我们的研究表明,与DENV不同,保守的14–23区不参与ZIKV衣壳-脂质液滴缔合的可能性。

更新日期:2020-08-12
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