sequence evolution of the intrinsically disordered and globular domains of a model viral oncoprotein序列的进化模型的内在无序和球状域病毒癌蛋白.pdfVIP

Sequence Evolution of the Intrinsically Disordered and Globular Domains of a Model Viral Oncoprotein ´ 1 2 1 3 Lucıa B. Chemes , Juliana Glavina , Leonardo G. Alonso , Cristina Marino-Buslje , Gonzalo de Prat- 1 ´ 2 Gay *, Ignacio E. Sanchez * ´ 1 Protein Structure-Function and Engineering Laboratory, Fundacion Instituto Leloir and IIBBA-CONICET, Buenos Aires, Argentina, 2 Protein Physiology Laboratory, ´ ´ Departamento de Quımica Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, Argentina, 3 Structural ´ Bioinformatics Laboratory. Fundacion Instituto Leloir and IIBBA-CONICET, Buenos Aires, Argentina Abstract In the present work, we have used the papillomavirus E7 oncoprotein to pursue structure-function and evolutionary studies that take into account intrinsic disorder and the conformational diversity of globular domains. The intrinsically disordered (E7N) and globular (E7C) domains of E7 show similar degrees of conservation and co-evolution. We found that E7N can be described in terms of conserved and coevolving linear motifs separated by variable linkers, while sequence evolution of E7C is compatible with the known homodimeric structure yet suggests other activities for the domain. Within E7N, inter-residue relationships such as residue co-evolution and restricted intermotif distances map functional coupling and co-occurrence of linear motifs that evolve in a coordinate manner. Within E7C, additional cysteine residues proximal to the zinc-binding site