Structure of a Reptilian Adenovirus Reveals a Phage Tailspike Fold Stabilizing a Vertebrate Virus Capsid

Abstract

Although non-human adenoviruses (AdVs) might offer solutions to problems posed by human AdVs as therapeutic vectors, little is known about their basic biology. In particular, there are no structural studies on the complete virion of any AdV with a non-mammalian host. We combine mass spectrometry, cryo-electron microscopy, and protein crystallography to characterize the composition and structure of a snake AdV (SnAdV-1, Atadenovirus genus). SnAdV-1 particles contain the genus-specific proteins LH3, p32k, and LH2, a previously unrecognized structural component. Remarkably, the cementing protein LH3 has a trimeric β helix fold typical of bacteriophage host attachment proteins. The organization of minor coat proteins differs from that in human AdVs, correlating with higher thermostability in SnAdV-1. These findings add a new piece to the intriguing puzzle of virus evolution, hint at the use of cell entry pathways different from those in human AdVs, and will help development of new, thermostable SnAdV-1-based vectors.

Target highlights from the first post‐PSI CASP experiment (CASP12, May–August 2016)

“…The Snake Atadenovirus 1 LH3 protein (CASP target T0909) was expressed in E. coli, crystallized, the structure was solved using SAD from a mercury derivative crystal and refined using native data of a different crystal form at 2.0 Å resolution. 84 Evidence of proteolysis was observed and is consistent with the first 25 residues missing from the experimentally determined structure (Figure 9). The structure revealed The b-sheets are named PB1, PB2 and PB3, following the nomenclature proposed by Mayans et al 86 Turns between b-strands are named T1 (between PB1 and PB2), T2 (between PB2 and PB3), and T3 (between PB3 and PB1).…”

“…The Snake Atadenovirus 1 LH3 protein (CASP target T0909) was expressed in E. coli , crystallized, the structure was solved using SAD from a mercury derivative crystal and refined using native data of a different crystal form at 2.0 Å resolution . Evidence of proteolysis was observed and is consistent with the first 25 residues missing from the experimentally determined structure (Figure ).…”

“…| 39 a compact, knob-like trimer of right-handed b-helices, as predicted bythe BetaWrap server 85. The missing part was evident when fitting the structure into an 11 Å cryo-EM map of SnAdV-1 84. Each LH3 monomer contains eleven b-helical rungs stacked on top of each other.…”

Adenoviruses across the animal kingdom: a walk in the zoo

“…SnAdV‐2 was detected in eastern corn snake, California kingsnake, and asp viper, and SnAdV‐3 in gopher snake . Full genome sequence of SnAdV‐1 has been published and its structure was also studied . One should keep in mind that all these AdVs have been found in captive‐bred snakes.…”

A hyperthermophilic phage decoration protein suggests common evolutionary origin with Herpesvirus Triplex proteins and an anti-CRISPR protein

“…Removal of D4 results in non-productive assembly of the tailspike trimer [53], most likely due to kinetic traps in the folding of the highly interdigitated -helix motifs found in the D1, D2, and D3 domains [73]. (We note that an Adenovirus uses the tailspike -helix fold as a decoration protein to stabilize the capsid three-fold vertices [74]. Thus, both the -tulip and -helix regions of the tailspike have evolved to stabilize the capsid.)…”