Conformational plasticity in folding of the E6*I protein, the major splicing product for the oncoprotein E6 from the high-risk human papillomavirus.

ANGELES HEER; ALONSO LEONARDO G.; DE PRAT-GAY GONZALO

Salta

Congreso; XXXIX Annual Meeting of the Argentinean Biophysical Society (SAB 2010); 2010

XXXIX Annual Meeting of the Argentinean Biophysical Society (SAB 2010)

E6*I is the most representative E6 spliced mRNA in HPV transformed cells, cervicalcancer cell lines and clinical samples and encode for the first 50 amino acid of the E6oncoprotein, including only half of the first Zn binding motif of the full length E6 protein.In this context, we want to characterize E6*I in solution in terms of folding, stability andZn binding properties.Depending on the pH of the solution, E6*I is capable of adopt an alpha-helix or a betasheetsecondary structure. As many small peptides do, E6*I maintains its structures troughformation of high molecular weight structures. At low pH, E6*I shares properties withamyloid-like structures. At pH near to neutrality, assembles into oligomers with high alphahelixcontent. Interestingly, addition of Zn precludes the oligomerzation of the sample andmaintains the protein as a single small molecule, a dimer.We show that E6*I dimerizes in the presence of Zn to form a cysteine coordinating zinchigh affinity center, rebuilding the zinc finger domain present in full length E6. Thisbinding inhibits the oxidation of two of its three cysteins that otherwise oxidize to form anintramolecular disulfide bridge.The conformational diversity observed for this molecule could regulate E6*I functionexpanding its biological relevance.