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Computational Analysis of Domains Vulnerable to HPV-16 E6 Oncoprotein and Corresponding Hot Spot Residues

[ Vol. 28 , Issue. 4 ]


Rabbiah Manzoor Malik*, Sahar Fazal and Mohammad Amjad Kamal   Pages 414 - 425 ( 12 )


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.


E6, hPV, cervical cancer, protein interactions, motifs, domains, e6AP, paxillin, tNF R1, elastic network models.


Capital University of Science and Technology, Islamabad, Capital University of Science and Technology, Islamabad, West China School of Nursing / Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan

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