Design of a PDZbody, a bivalent binder of the E6 protein from human papillomavirus

Scientific Reports

Volumn 5, Issue , 2015, Pages

  Karlsson, O Andreas ^a   Ramirez, Juan ^b   Öberg, Daniel ^a   Malmqvist, Tony ^a   Engström, Åke ^a   Friberg, Maria ^a   Chi, Celestine N ^a   Widersten, Mikael ^c   Travé, Gilles ^b   Nilsson, Mikael T I ^c   Jemth, Per ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg   (France)

^c UPPSALA UNIVERSITY   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

DLG1 PROTEIN, HUMAN; DNA BINDING PROTEIN; E6 PROTEIN, HUMAN PAPILLOMAVIRUS TYPE 16; E6 PROTEIN, HUMAN PAPILLOMAVIRUS TYPE 18; MEMBRANE PROTEIN; ONCOPROTEIN; PEPTIDE LIBRARY; PROTEIN BINDING; RECOMBINANT PROTEIN; REPRESSOR PROTEIN; SIGNAL TRANSDUCING ADAPTOR PROTEIN;

AMINO ACID SEQUENCE; BINDING SITE; CHEMISTRY; ESCHERICHIA COLI; GENE EXPRESSION; GENETICS; HELA CELL LINE; HUMAN; HUMAN PAPILLOMAVIRUS TYPE 16; HUMAN PAPILLOMAVIRUS TYPE 18; IMMUNOPRECIPITATION; METABOLISM; MOLECULAR GENETICS; MOLECULAR MODEL; PDZ DOMAIN; PEPTIDE LIBRARY; PROTEIN SECONDARY STRUCTURE;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; AMINO ACID SEQUENCE; BINDING SITES; DNA-BINDING PROTEINS; ESCHERICHIA COLI; GENE EXPRESSION; HELA CELLS; HUMAN PAPILLOMAVIRUS 16; HUMAN PAPILLOMAVIRUS 18; HUMANS; IMMUNOPRECIPITATION; MEMBRANE PROTEINS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; ONCOGENE PROTEINS, VIRAL; PDZ DOMAINS; PEPTIDE LIBRARY; PROTEIN BINDING; PROTEIN STRUCTURE, SECONDARY; RECOMBINANT PROTEINS; REPRESSOR PROTEINS;

EID: 84925435005     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep09382     Document Type: Article

References (53)

1. Bzhalava, D., Eklund, C. & Dillner, J. International standardization and classification of human papillomavirus types. Virology 476, 341-344 (2015).
2. Doorbar, J. et al. The biology and life-cycle of human papillomaviruses. Vaccine 30 Suppl 5, F55-70 (2012).
3. Moody, C. A. & Laimins, L. A. Human papillomavirus oncoproteins: pathways to transformation. Nat. Rev. Cancer 10, 550-560 (2010).
4. Magaldi, T. G. et al. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation. Virology 422, 114-124 (2012).
5. Manzo-Merino, J., Thomas, M., Fuentes-Gonzalez, A. M., Lizano, M. & Banks, L. HPV E6 oncoprotein as a potential therapeutic target in HPV related cancers. Expert Opin. Ther. Targets 17, 1357-1368 (2013).
6. Goodwin, E. C. & DiMaio, D. Repression of human papillomavirus oncogenes in HeLa cervical carcinoma cells causes the orderly reactivation of dormant tumor suppressor pathways. Proc. Natl. Acad. Sci. U. S. A. 97, 12513-12518 (2000).
7. Horner, S. M., DeFilippis, R. A., Manuelidis, L. & DiMaio, D. Repression of the Human Papillomavirus E6 Gene Initiates p53-Dependent, Telomerase-Independent Senescence and Apoptosis in HeLa Cervical Carcinoma Cells. J. Virol. 78, 4063-4073 (2004).
8. Morrison, M. A. et al. Targeting the human papillomavirus E6 and E7 oncogenes through expression of the bovine papillomavirus type 1 E2 protein stimulates cellular motility. J. Virol. 85, 10487-10498 (2011).
9. Togtema, M. et al. Sonoporation Delivery of Monoclonal Antibodies against Human Papillomavirus 16 E6 Restores p53 Expression in Transformed Cervical Keratinocytes. PLoS ONE 7, e50730 (2012).
10. Courtête, J. et al. Suppression of cervical carcinoma cell growth by intracytoplasmic codelivery of anti-oncoprotein E6 antibody and small interfering RNA. Mol. Cancer Ther. 6, 1728-1735 (2007).
11. Binz, H. K. et al. High-affinity binders selected from designed ankyrin repeat protein libraries. Nat. Biotechnol. 22, 575-582 (2004).
12. Nygren, P.-A. Alternative binding proteins: affibody binding proteins developed from a small three-helix bundle scaffold. FEBS J. 275, 2668-2676 (2008).
13. Corson, T. W., Aberle, N. & Crews, C. M. Design and Applications of Bifunctional Small Molecules: Why Two Heads Are Better Than One. ACS Chem. Biol. 3, 677-692 (2008).
14. Gower, C. M., Chang, M. E. K. & Maly, D. J. Bivalent inhibitors of protein kinases. Crit. Rev. Biochem. Mol. Biol. doi:10.3109/10409238.2013.875513 (2014).
15. Zhou, H.-X. Quantitative Account of the Enhanced Affinity of Two Linked scFvs Specific for Different Epitopes on the Same Antigen. J. Mol. Biol. 329, 1-8 (2003).
16. Bach, A. et al. Design and synthesis of highly potent and plasma-stable dimeric inhibitors of the PSD-95-NMDA receptor interaction. Angew. Chem. Int. Ed Engl. 48, 9685-9689 (2009).
17. Bach, A. et al. A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage. Proc. Natl. Acad. Sci. U. S. A. 109, 3317-3322 (2012).
18. Chi, C. N. et al. Deciphering the kinetic binding mechanism of dimeric ligands using a potent plasma-stable dimeric inhibitor of postsynaptic density protein-95 as an example. J. Biol. Chem. 285, 28252-28260 (2010).
19. Chen, J. J., Hong, Y., Rustamzadeh, E., Baleja, J. D. & Androphy, E. J. Identification of an alpha helical motif sufficient for association with papillomavirus E6. J. Biol. Chem. 273, 13537-13544 (1998).
20. Huibregtse, J. M., Scheffner, M. & Howley, P. M. Localization of the E6-AP regions that direct human papillomavirus E6 binding, association with p53, and ubiquitination of associated proteins. Mol. Cell. Biol. 13, 4918-4927 (1993).
21. Scheffner, M., Huibregtse, J. M., Vierstra, R. D. & Howley, P. M. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 75, 495-505 (1993).
22. Wells, J. A. & McClendon, C. L. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature 450, 1001-1009 (2007).
23. Malecka, K. A. et al. Identification and characterization of small molecule human papillomavirus E6 inhibitors. ACS Chem. Biol. 9, 1603-1612, doi:10.1021/cb500229d (2014).
24. Pim, D. et al. Human papillomaviruses and the specificity of PDZ domain targeting: HPV PDZ interactions. FEBS J. 279, 3530-3537 (2012).
25. Kiyono, T. et al. Binding of high-risk human papillomavirus E6 oncoproteins to the human homologue of the Drosophila discs large tumor suppressor protein. Proc. Natl. Acad. Sci. U. S. A. 94, 11612-11616 (1997).
26. Lee, S. S., Weiss, R. S. & Javier, R. T. Binding of human virus oncoproteins to hDlg/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein. Proc. Natl. Acad. Sci. U. S. A. 94, 6670-6675 (1997).
27. Zhang, Y. et al. 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, 3618-3626 (2007).
28. Liu, Y., Henry, G. D., Hegde, R. S. & Baleja, J. D. Solution structure of the hDlg/SAP97 PDZ2 domain and its mechanism of interaction with HPV-18 papillomavirus E6 protein. Biochemistry 46, 10864-10874 (2007).
29. Chi, C. N. et al. A sequential binding mechanism in a PDZ domain. Biochemistry 48, 7089-7097 (2009).
30. Chi, C. N. et al. Biophysical Characterization of the Complex between Human Papillomavirus E6 Protein and Synapse-associated Protein 97. J. Biol. Chem. 286, 3597-3606 (2011).
31. Hultqvist, G. et al. Energetic pathway sampling in a protein interaction domain. Structure 21, 1193-1202 (2013).
32. Haq, S. R. et al. The plastic energy landscape of protein folding: a triangular folding mechanism with an equilibrium intermediate for a small protein domain. J. Biol. Chem. 285, 18051-18059 (2010).
33. Hultqvist, G. et al. Tolerance of protein folding to a circular permutation in a PDZ domain. PloS One 7, e50055 (2012).
34. Ivarsson, Y. Plasticity of PDZ domains in ligand recognition and signaling. FEBS Lett. 586, 2638-2647 (2012).
35. Jemth, P. & Gianni, S. PDZ domains: folding and binding. Biochemistry (Mosc.) 46, 8701-8708 (2007).
36. Ernst, A. et al. Coevolution of PDZ domain-ligand interactions analyzed by high-throughput phage display and deep sequencing. Mol. Biosyst. 6, 1782 (2010).
37. Ferrer, M. et al. Directed evolution of PDZ variants to generate high-affinity detection reagents. Protein Eng. Des. Sel. 18, 165-173 (2005).
38. Nilsson, M. T., Mossing, M. C. & Widersten, M. Functional expression and affinity selection of single-chain cro by phage display: isolation of novel DNA-binding proteins. Protein Eng. 13, 519-526 (2000).
39. Dardel, F., Davis, A. L., Laue, E. D. & Perham, R. N. Three-dimensional structure of the lipoyl domain from Bacillus stearothermophilus pyruvate dehydrogenase multienzyme complex. J. Mol. Biol. 229, 1037-1048 (1993).
40. Ivarsson, Y. et al. Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes. Proc. Natl. Acad. Sci. U. S. A. 111, 2542-2547 (2014).
41. Wiedemann, U. et al. Quantification of PDZ domain specificity, prediction of ligand affinity and rational design of super-binding peptides. J. Mol. Biol. 343, 703-718 (2004).
42. Zanier, K. et al. Structural Basis for Hijacking of Cellular LxxLL Motifs by Papillomavirus E6 Oncoproteins. Science 339, 694-698 (2013).
43. Liu, Y., Liu, Z., Androphy, E., Chen, J. & Baleja, J. D. Design and characterization of helical peptides that inhibit the E6 protein of papillomavirus. Biochemistry 43, 7421-7431 (2004).
44. Zanier, K. et al. Kinetic analysis of the interactions of human papillomavirus E6 oncoproteins with the ubiquitin ligase E6AP using surface plasmon resonance. J. Mol. Biol. 349, 401-412 (2005).
45. Nominé, Y. et al. A strategy for optimizing the monodispersity of fusion proteins: application to purification of recombinant HPV E6 oncoprotein. Protein Eng. 14, 297-305 (2001).
46. Zanier, K. et al. Solution structure analysis of the HPV16 E6 oncoprotein reveals a self-association mechanism required for E6-mediated degradation of p53. Structure 20, 604-617 (2012).
47. Nominé, Y. et al. Structural and functional analysis of E6 oncoprotein: insights in the molecular pathways of human papillomavirus-mediated pathogenesis. Mol. Cell 21, 665-678 (2006).
48. Scheffner, M., Werness, B. A., Huibregtse, J. M., Levine, A. J. & Howley, P. M. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63, 1129-1136 (1990).
49. Werness, B. A., Levine, A. J. & Howley, P. M. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 248, 76-79 (1990).
50. Massimi, P., Gammoh, N., Thomas, M. & Banks, L. HPV E6 specifically targets different cellular pools of its PDZ domain-containing tumour suppressor substrates for proteasome-mediated degradation. Oncogene 23, 8033-8039 (2004).
51. Karlsson, O. A., Chi, C. N., Engström, A. & Jemth, P. The transition state of coupled folding and binding for a flexible b-finger. J. Mol. Biol. 417, 253-261 (2012).
52. Malatesta, F. The study of bimolecular reactions under non-pseudo-first order conditions. Biophys. Chem. 116, 251-256 (2005).
53. Velazquez-Campoy, A., Leavitt, S. A. & Freire, E. Characterization of protein-protein interactions by isothermal titration calorimetry. Methods Mol. Biol. 261, 35-54 (2004).