Molecular mechanisms of the viral encoded chaperone 100K in capsid folding and assembly of adenovirus

Abstract

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.