Evidence for the role of His-142 of protein 1C in the acid-induced disassembly of foot-and-mouth disease virus capsids
Evidence for the role of His-142 of protein 1C in the acid-induced disassembly of foot-and-mouth disease virus capsids
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DOI：
10.1099/0022-1317-80-8-1911
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发表时间：
1999-08-01
影响因子：
3.8
通讯作者：
King, AMQ
中科院分区：
文献类型：
--
作者：
Ellard, FM;Drew, J;King, AMQ
口蹄疫病毒（FMDV）衣壳在弱酸性条件下固有地不稳定，在pH值6.5的区域中解离成五聚体，释放蛋白1A和病毒RNA。这种酸诱导的分解被认为是病毒基因组进入宿主细胞所必需的。以前的工作已经强调了组氨酸-α-螺旋电荷偶极相互作用在五聚体之间的双重对称轴，并建议这种相互作用在酸诱导的拆卸中发挥作用。该理论的有效性现在已经通过将蛋白1C的相关残基His-142转化为Arg、Phe和Asp来测试。通过使用先前描述的牛痘病毒表达系统来研究这种变化的影响，其中FMDV衣壳蛋白的合成和加工导致衣壳的自组装。与组氨酸-α-螺旋电荷偶极理论一致，发现精氨酸突变体中的组装大大减少，而天冬氨酸突变体的衣壳在酸性条件下比野生型稳定得多。在苯丙氨酸突变体中获得了异常但酸稳定的复合物。
Foot-and-mouth disease virus (FMDV) capsids are inherently labile under mildly acidic conditions, dissociating to pentamers at pH values in the region of 6.5, with the release of protein 1A and the viral RNA. This acid-induced disassembly is thought to be required for the entry of the virus genome into the host cell. Previous work has highlighted a histidine-alpha-helix charge-dipole interaction at the twofold axes of symmetry between pentamers and has suggested that this interaction plays a role in acid-induced disassembly. The validity of this theory has now been tested by converting the implicated residue, His-142 of protein 1C, to Arg, Phe and Asp, The effects of such changes were studied by using a previously described vaccinia virus expression system, in which synthesis and processing of FMDV capsid proteins results in the self-assembly of capsids, In agreement with the histidine-alpha-helix charge-dipole theory, assembly in the arginine mutant was found to be greatly reduced, while capsids of the aspartic acid mutant were considerably more stable under acidic conditions than the wild-type. Aberrant but acid-stable complexes were obtained in the phenylalanine mutant.