Structural determinants within the adenovirus early region 1A protein spacer region necessary for tumourigenesis.

It has long been established that group-A adenoviruses (HAdV-A12, -A18 and -A31) can cause tumours in new-born rodents with tumourigenicity related to the presence of a unique spacer region located between conserved regions 2 and 3 within the HAdV-A12E1A protein. Group B adenoviruses are weakly oncogenic whereas most of the remaining human adenoviruses are non-oncogenic. In order to understand better the relationship between the structure of the AdE1A spacer region and oncogenicity of HAdVs the structure of synthetic peptides identical or very similar to the adenovirus 12 E1A spacer region were determined to be α-helical using NMR spectroscopy. This contrasts significantly with some previous suggestions that this region is unstructured. Using available predictive algorithms, the structures of spacer regions from other E1As were also examined and the extent of predicted α-helix was found to correlate reasonably well with the tumorigenicity of the respective viruses. We suggest that this may represent an, as yet unknown, binding site for a partner protein required for tumourigenesis.ImportanceThis research analysed small peptides equivalent to a region within the human adenovirus early region 1A protein that confers, in part, tumour inducing properties to varying degrees on several viral strains in rats and mice. The oncogenic spacer region is alpha-helical, which contrasts with previous suggestions that this region is unstructured. The helix is characterised by a stretch of amino acids rich in alanine residues that are organised into a hydrophobic or 'water-hating' surface that is considered to form a major site of interaction with cellular protein targets that mediate tumour formation. The extent of alpha-helix in E1A from other adenovirus species can be correlated to a limited degree to the tumourigenicity of that virus. Some serotypes show significant differences in predicted structural propensity suggesting the amino acid type and physicochemical properties are also of importance.