2i04 Citations

Structures of a human papillomavirus (HPV) E6 polypeptide bound to MAGUK proteins: mechanisms of targeting tumor suppressors by a high-risk HPV oncoprotein.

J Virol 81 3618-26 (2007)
Related entries: 2i0i, 2i0l

Cited: 86 times
EuropePMC logo PMID: 17267502

Abstract

Human papillomavirus (HPV) E6 oncoprotein targets certain tumor suppressors such as MAGI-1 and SAP97/hDlg for degradation. A short peptide at the C terminus of E6 interacts specifically with the PDZ domains of these tumor suppressors, which is a property unique to high-risk HPVs that are associated with cervical cancer. The detailed recognition mechanisms between HPV E6 and PDZ proteins are unclear. To understand the specific binding of cellular PDZ substrates by HPV E6, we have solved the crystal structures of the complexes containing a peptide from HPV18 E6 bound to three PDZ domains from MAGI-1 and SAP97/Dlg. The complex crystal structures reveal novel features of PDZ peptide recognition that explain why high-risk HPV E6 can specifically target these cellular tumor suppressors for destruction. Moreover, a new peptide-binding loop on these PDZs is identified as interacting with the E6 peptide. Furthermore, we have identified an arginine residue, unique to high-risk HPV E6 but outside the canonical core PDZ recognition motif, that plays an important role in the binding of the PDZs of both MAGI-I and SAP97/Dlg, the mutation of which abolishes E6's ability to degrade the two proteins. Finally, we have identified a dimer form of MAGI-1 PDZ domain 1 in the cocrystal structure with E6 peptide, which may have functional relevance for MAGI-1 activity. In addition to its novel insights into the biochemistry of PDZ interactions, this study is important for understanding HPV-induced oncogenesis; this could provide a basis for developing antiviral and anticancer compounds.

Reviews - 2i04 mentioned but not cited (1)

  1. The critical protein interactions and structures that elicit growth deregulation in cancer and viral replication. Ou HD, May AP, O'Shea CC. Wiley Interdiscip Rev Syst Biol Med 3 48-73 (2011)

Articles - 2i04 mentioned but not cited (8)



Reviews citing this publication (25)

  1. Papillomavirus E6 oncoproteins. Vande Pol SB, Klingelhutz AJ. Virology 445 115-137 (2013)
  2. Mucosal and Cutaneous Human Papillomavirus Infections and Cancer Biology. Gheit T. Front Oncol 9 355 (2019)
  3. Emerging theme: cellular PDZ proteins as common targets of pathogenic viruses. Javier RT, Rice AP. J Virol 85 11544-11556 (2011)
  4. Human papillomaviruses, cervical cancer and cell polarity. Thomas M, Narayan N, Pim D, Tomaić V, Massimi P, Nagasaka K, Kranjec C, Gammoh N, Banks L. Oncogene 27 7018-7030 (2008)
  5. Functional Roles of E6 and E7 Oncoproteins in HPV-Induced Malignancies at Diverse Anatomical Sites. Tomaić V. Cancers (Basel) 8 E95 (2016)
  6. The Human Papillomavirus E6 PDZ Binding Motif: From Life Cycle to Malignancy. Ganti K, Broniarczyk J, Manoubi W, Massimi P, Mittal S, Pim D, Szalmas A, Thatte J, Thomas M, Tomaić V, Banks L. Viruses 7 3530-3551 (2015)
  7. The emerging contribution of sequence context to the specificity of protein interactions mediated by PDZ domains. Luck K, Charbonnier S, Travé G. FEBS Lett 586 2648-2661 (2012)
  8. Human papillomavirus E6 and E7 oncoproteins as risk factors for tumorigenesis. Ganguly N, Parihar SP. J Biosci 34 113-123 (2009)
  9. PDZ domains: the building blocks regulating tumorigenesis. Subbaiah VK, Kranjec C, Thomas M, Banks L. Biochem J 439 195-205 (2011)
  10. Human papillomaviruses and the specificity of PDZ domain targeting. Pim D, Bergant M, Boon SS, Ganti K, Kranjec C, Massimi P, Subbaiah VK, Thomas M, Tomaić V, Banks L. FEBS J 279 3530-3537 (2012)
  11. Viral oncogenes, noncoding RNAs, and RNA splicing in human tumor viruses. Zheng ZM. Int J Biol Sci 6 730-755 (2010)
  12. Regulation of the Wnt/β-Catenin Signaling Pathway by Human Papillomavirus E6 and E7 Oncoproteins. Bello JO, Nieva LO, Paredes AC, Gonzalez AM, Zavaleta LR, Lizano M. Viruses 7 4734-4755 (2015)
  13. Human tumour viruses and the deregulation of cell polarity in cancer. Banks L, Pim D, Thomas M. Nat Rev Cancer 12 877-886 (2012)
  14. Human papillomavirus E6 and E7: What remains? Vats A, Trejo-Cerro O, Thomas M, Banks L. Tumour Virus Res 11 200213 (2021)
  15. Ligand binding by PDZ domains. Chi CN, Bach A, Strømgaard K, Gianni S, Jemth P. Biofactors 38 338-348 (2012)
  16. Oncogenes and RNA splicing of human tumor viruses. Ajiro M, Zheng ZM. Emerg Microbes Infect 3 e63 (2014)
  17. Human papilloma virus (HPV) and host cellular interactions. Mammas IN, Sourvinos G, Giannoudis A, Spandidos DA. Pathol Oncol Res 14 345-354 (2008)
  18. Molecular mechanisms in progression of HPV-associated cervical carcinogenesis. Gupta SM, Mania-Pramanik J. J Biomed Sci 26 28 (2019)
  19. Specificity in PDZ-peptide interaction networks: Computational analysis and review. Amacher JF, Brooks L, Hampton TH, Madden DR. J Struct Biol X 4 100022 (2020)
  20. DNA Oncogenic Virus-Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations. Kgatle MM, Spearman CW, Kalla AA, Hairwadzi HN. Oxid Med Cell Longev 2017 3179421 (2017)
  21. Structural Insights in Multifunctional Papillomavirus Oncoproteins. Suarez I, Trave G. Viruses 10 E37 (2018)
  22. HPV Oncoproteins and the Ubiquitin Proteasome System: A Signature of Malignancy? Đukić A, Lulić L, Thomas M, Skelin J, Bennett Saidu NE, Grce M, Banks L, Tomaić V. Pathogens 9 E133 (2020)
  23. HPV E6 oncoprotein as a potential therapeutic target in HPV related cancers. Manzo-Merino J, Thomas M, Fuentes-Gonzalez AM, Lizano M, Banks L. Expert Opin Ther Targets 17 1357-1368 (2013)
  24. Upsetting the Balance: When Viruses Manipulate Cell Polarity Control. Thomas M, Banks L. J Mol Biol 430 3481-3503 (2018)
  25. A New Story of the Three Magi: Scaffolding Proteins and lncRNA Suppressors of Cancer. Kotelevets L, Chastre E. Cancers (Basel) 13 4264 (2021)

Articles citing this publication (52)



Related citations provided by authors (1)