Li Haining, Shao Luyuan, Liu Zhe, Liu Qi, Xiang Ye
Center for Infectious Disease Research, Beijing Frontier Research Center for Biological Structure, School of Basic Medical Sciences, Tsinghua University, Beijing, China.
SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine, Shanxi Medical University, Taiyuan, Shanxi Province, China.
Nat Commun. 2025 Apr 29;16(1):4013. doi: 10.1038/s41467-025-59301-4.
Adenovirus is an icosahedral, non-enveloped DNA virus that infects humans and other animals. The capsid of adenovirus is mainly assembled by the major capsid protein hexon. Folding and assembly of hexon require the viral encoded chaperone 100K, of which the detailed structure and chaperoning mechanism remain unknown. Here, we report the cryoEM structure of 100K in complex with a pre-mature hexon trimer. The structure shows that 100K dimers bind to the bottom double jelly-roll domains of the pre-mature hexon, mainly through a hook-like domain and a loop extruded from the dimerization domain. Additionally, a groove formed at the dimerization interface of 100K accommodates the N-terminal fragment 49-53 of an adjacent hexon protomer. Mutagenesis studies indicate that the interactions at the jelly-roll domain and the N-terminus of hexon are all essential for the proper folding and assembly of hexon. 100K binds and stabilizes the partially folded hexon, preventing premature aggregation of hexon, promoting the folding of the hexon top insertion loops, and facilitating hexon trimerization.
腺病毒是一种二十面体、无包膜的DNA病毒，可感染人类和其他动物。腺病毒的衣壳主要由主要衣壳蛋白六邻体组装而成。六邻体的折叠和组装需要病毒编码的伴侣蛋白100K，其详细结构和伴侣机制尚不清楚。在此，我们报告了100K与未成熟六邻体三聚体复合物的冷冻电镜结构。该结构显示，100K二聚体主要通过一个钩状结构域和一个从二聚化结构域伸出的环与未成熟六邻体的底部双果冻卷结构域结合。此外，在100K的二聚化界面形成的一个凹槽容纳相邻六邻体原聚体的N端片段49-53。诱变研究表明，六邻体果冻卷结构域和N端的相互作用对于六邻体的正确折叠和组装都是必不可少的。100K结合并稳定部分折叠的六邻体，防止六邻体过早聚集，促进六邻体顶部插入环的折叠，并促进六邻体三聚化。
