Unstructural biology of the papillomavirus E7 oncoprotein

CHEMES, L.B.; GLAVINA, J; ALONSO, L.G.; MARINO BUSLJE, C; DE PRAT-GAY, G.; SANCHEZ, IE

Basel

Congreso; ECCB12 11th European Conference on Computational Biology; 2012

Swiss Institute of Bioinformatics

Motivation: We use the papillomavirus E7 oncoprotein to pursue structure-function and evolutionary studies that take into account intrinsic disorder and the conformational diversity of globular domains. Results: The intrinsically disordered (E7N) and globular (E7C) domains of E7 show similar degrees of conservation and coevolution. E7N can be described in terms of conserved and coevolving linear motifs separated by variable linkers. Sequence evolution of E7C is compatible with the known homodimeric structure yet suggests other activities for the domain. Additional cysteine residues in E7C proximal to the zinc-binding site may allow redox regulation of E7 function. Moreover, we describe a conserved binding site for disordered domains on the surface of E7C and suggest a putative target linear motif. Both homodimerization and peptide binding activities of E7C are also present in the distantly related host PHD domains. Finally, we integrate the multiple activities and conformations of E7 into a hierarchy of structurefunction relationships.