Near Atomic Structure of an Atadenovirus Reveals a Conserved Capsid-Binding Motif and Intergenera Variations in Cementing Proteins

Abstract

Little is known about the basic biology of non-human adenoviruses, which could be alternative vectors free of issues posed by preexisting immunity to human adenoviruses. We present the cryo-EM structure of a lizard atadenovirus, LAdV-2, at 3.4 [A] resolution. This is the first high resolution structure of an adenovirus with non-mammalian host, and of an adenovirus not belonging to the Mastadenovirus genus. Atadenovirus capsids contain genus specific proteins LH3, p32k, and LH2, and are more thermostable than the more studied human adenoviruses. We find a large conformational difference in the internal vertex protein IIIa between mast- and atadenoviruses, induced by the presence of an extended polypeptide in the region. This polypeptide, as well as -helical clusters located beneath the icosahedral facet, likely correspond to proteins LH2 and p32k. The external genus specific protein LH3, with a trimeric {beta}-helix fold typical of bacteriophage host attachment proteins, contacts the hexon shell surface via a triskelion structure identical to that used by protein IX in human AdV, revealing a conserved capsid-binding motif and a possible gene duplication event. Altogether, this work shows how the network of minor coat proteins differs between AdV genera and relates to virus evolution and capsid stability properties.