Redox state and metal binding properties of HPV16 E7 oncoprotein

ALONSO, L.G; GARCIA ALAI, M.M; SMAL, C; PRAT GAY, G

Angra dos Reis, RJ, Brazil.

Congreso; First Latin America Protein Society Meeting; 2004

Human papillomaviruses are small non-enveloped ADN viruses involved in cervix cancer development. One of the two major transforming proteins, E7, is a metalloprotein that binds one Zn atom per monomer, shares some properties with the natively unfolded proteins or intrinsically unordered proteins and shows a  broad range of cellular targets including the retinoblatoma  tumor suppressor protein Rb. Any structure of E7 protein has been determined so far, due to its dynamic, non structured conformation and its complex biochemical behavior which includes increase in its secondary structure amount upon pH, salt and temperature variations and changes in its oligomerization state going through monomer, dimmer to high weight ordered oligomers. E7 contains seven cysteine residues, four of them are involved in Zn coordination  and  the recombinant purified protein showed that all cysteines residues are in its reduced state: thiol(ate) state. Changing redox conditions by using glutatione redox buffers and H2O2  exposure leads to different cystein modifications and produces reversible Zn release of the protein. The redox potential of these processes are compatible with physiological values and could act as redox switches controlling E7 assembly. We propose that E7 protein can sense oxidative stressors and Zn availability to provide an on/off regulation of its functions.