Structures of adenovirus incomplete particles clarify capsid architecture and show maturation changes of packaging protein L1 52/55k

© 2015, American Society for Microbiology. Adenovirus is one of themost complex icosahedral, nonenveloped viruses. Even after its structure was solved at near-atomic resolution by both cryo-electronmicroscopy and X-ray crystallography, the location ofminor coat proteins is still a subject of debate. The elaborated capsid architecture is the product of a correspondingly complex assembly process, about whichmany aspects remain unknown. Genome encapsidation involves the concerted action of five virus proteins, and proteolytic processing by the virus protease is needed to prime the virion for sequential uncoating. Protein L1 52/55k is required for packaging, and multiple cleavages by thematuration protease facilitate its release fromthe nascent virion. Light-density particles are routinely produced in adenovirus infections and are thought to represent assembly intermediates. Here, we present themolecular and structural characterization of two different types of human adenovirus light particles produced by amutant with delayed pack- aging. We show that these particles lack core polypeptide V but do not lack the density corresponding to this protein in the X-ray structure, thereby adding support to the adenovirus cryo-electronmicroscopymodel. The two types of light particles present different degrees of proteolytic processing. Their structures provide the first glimpse of the organization of L1 52/55k protein inside the capsid shell and of how this organization changes upon partialmaturation. Immature, full-length L1 52/55k is poised beneath the vertices to engage the virus genome. Upon proteolytic processing, L1 52/55k disengages fromthe capsid shell, facili- tating genome release during uncoating.