Evolution of linear motifs within the papillomavirus E7 oncoprotein

CHEMES, L.V.; GLAVINA, J.; FAIVOVICH, J.; PRAT-GAY, G.; SANCHEZ, I.E.

JOURNAL OF MOLECULAR BIOLOGY

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2012 vol. 422 p. 336 - 346

0022-2836

Many protein functions can be traced to linear sequence motifs of less thanfive residues, which are often found within intrinsically disordereddomains. In spite of their prevalence, their role in protein evolution is onlybeginning to be understood. The study of papillomaviruses has providedmany insights on the evolution of protein structure and function. We havechosen the papillomavirus E7 oncoprotein as a model system for theevolution of functional linear motifs. The multiple functions of E7 proteinsfrom paradigmatic papillomavirus types can be explained to a large extentin terms of five linear motifs within the intrinsically disordered N-terminaldomain and two linear motifs within the globular homodimeric C-terminaldomain. We examined the motif inventory of E7 proteins from over 200known papillomavirus types and found that the motifs reported forparadigmatic papillomavirus types are absent from many uncharacterizedE7 proteins. Several motif pairs occur more often than expected, suggestingthat linear motifs may evolve and function in a cooperative manner. The E7linear motifs have appeared or disappeared multiple times duringpapillomavirus evolution, confirming the evolutionary plasticity of shortfunctional sequences. Four of the motifs appeared several times duringpapillomavirus evolution, providing direct evidence for convergentevolution. Interestingly, the evolution pattern of a motif is independent ofits location in a globular or disordered domain. The correlation between thepresence of some motifs and virus host specificity and tissue tropism suggeststhat linear motifs play a role in the adaptive evolution of papillomaviruses.