Bailey Graham D, Hyun Jae K, Mitra Alok K, Kingston Richard L
School of Biological Sciences, University of Auckland, Auckland, New Zealand.
Structure. 2009 May 13;17(5):737-48. doi: 10.1016/j.str.2009.03.010.
In mature retroviral particles, the capsid protein (CA) forms a shell encasing the viral replication complex. Human immunodeficiency virus (HIV) CA dimerizes in solution, through its C-terminal domain (CTD), and this interaction is important for capsid assembly. In contrast, other retroviral capsid proteins, including that of Rous sarcoma virus (RSV), do not dimerize with measurable affinity. Here we show, using X-ray crystallography and other biophysical methods, that acidification causes RSV CA to dimerize in a fashion analogous to HIV CA, and that this drives capsid assembly in vitro. A pair of aspartic acid residues, located within the CTD dimer interface, explains why dimerization is linked to proton binding. Our results show that despite overarching structural similarities, the intermolecular forces responsible for forming and stabilizing the retroviral capsid differ markedly across retroviral genera. Our data further suggest that proton binding may regulate RSV capsid assembly, or modulate stability of the assembled capsid.
在成熟的逆转录病毒颗粒中，衣壳蛋白（CA）形成一个包裹病毒复制复合体的外壳。人类免疫缺陷病毒（HIV）的CA在溶液中通过其C末端结构域（CTD）二聚化，这种相互作用对衣壳组装很重要。相比之下，其他逆转录病毒的衣壳蛋白，包括劳氏肉瘤病毒（RSV）的衣壳蛋白，不会以可测量的亲和力二聚化。在这里，我们使用X射线晶体学和其他生物物理方法表明，酸化会导致RSV的CA以类似于HIV的CA的方式二聚化，并且这会在体外驱动衣壳组装。位于CTD二聚体界面内的一对天冬氨酸残基解释了二聚化为何与质子结合相关。我们的结果表明，尽管总体结构相似，但不同逆转录病毒属中负责形成和稳定逆转录病毒衣壳的分子间力存在显著差异。我们的数据进一步表明，质子结合可能调节RSV衣壳组装，或调节组装后衣壳的稳定性。
