Background: Human Papilloma Virus (HPV) is the primary cause of cancers in cervix,
head and neck regions. Oncoprotein E6 of HPV-16, after infecting human body, alters host protein-
protein interaction networks. E6 interacts with several proteins, causing the infection to
progress into cervical cancer. The molecular basis for these interactions is the presence of short linear
peptide motifs on E6 identical to those on human proteins.
Methods: Motifs of LXXLL and E/DLLL/V-G after identification on E6, were analyzed for their
dynamic fluctuations by use of elastic network models. Correlation analysis of amino acid residues
of E6 was also performed in specific regions of motifs.
Results: Arginine, Leucine, Glutamine, Threonine and Glutamic acid have been identified as hot
spot residues of E6 which can subsequently provide a platform for drug designing and understanding
of pathogenesis of cervical cancer. These amino acids play a significant role in stabilizing interactions
with host proteins, ultimately causing infections and cancers.
Conclusion: Our study validates the role of linear binding motifs of E6 of HPV in interacting with
these proteins as an important event in the propagation of HPV in human cells and its transformation
into cervical cancer. The study further predicts the domains of protein kinase and armadillo as
part of the regions involved in the interaction of E6AP, Paxillin and TNF R1, with viral E6.