Comparative structural studies on Bovine papillomavirus E6 oncoproteins: Novel insights into viral infection and cell...

Bovine papillomavirus (BPV) infects cattle cells worldwide, leading to hyperproliferative lesions and the potential development of cancer, driven by E5, E6, and E7 oncoproteins along with other cofactors. E6 oncoprotein binds experimentally to various proteins, primarily paxillin and MAML1, as well as hMCM7 and CBP/p300. However, the molecular and structural mechanisms underlying BPV-induced malignant transformation remain unclear. Therefore, we have modeled the E6 oncoprotein structure from non-oncogenic BPV-5 and compared them with oncogenic BPV-1 to assess the relationship between structural features and oncogenic potential. Our analysis elucidated crucial structural aspects of E6, highlighting both conserved elements across genotypes and genotype-specific variations potentially implicated in the oncogenic process, particularly concerning primary target interactions. Additionally, we predicted the location of the hMCM7 binding site on the N-terminal of BPV-5 E6. This study enhances our understanding of the structural characteristics of BPV E6 oncoproteins and their interactions with host proteins, clarifying structural differences and similarities between high and low-risk BPVs. This is important to understand better the mechanisms involved in cell transformation in BPV infection, which could be used as a possible target for therapy.