Interplay between sequence, structure and linear motifs in the adenovirus E1A hub protein.
Glavina, J., Roman, E. A., Espada, R., de Prat-Gay, G., Chemes, L. B. and Sanchez, I. E.
Universidad de Buenos Aires. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Quimica Biologica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN). Facultad de Ciencias Exactas y Naturales. Laboratorio de Fisiologia de Proteinas. Buenos Aires, Argentina.
Instituto de Quimica y Fisico-Quimica Biologicas, Universidad de Buenos Aires, Junin 956, 1113AAD, Buenos Aires, Argentina.
Protein Structure-Function and Engineering Laboratory, Fundacion Instituto Leloir and IIBBA-CONICET, Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Investigaciones Biotecnologicas IIB-INTECH, Universidad Nacional de San Martin, San Martin, Buenos Aires, Argentina; Departamento de Fisiologia y Biologia Molecular y Celular (DFBMC), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina. Electronic address: lchemes@iib.unsam.edu.ar.
Universidad de Buenos Aires. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Quimica Biologica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN). Facultad de Ciencias Exactas y Naturales. Laboratorio de Fisiologia de Proteinas. Buenos Aires, Argentina. Electronic address: isanchez@qb.fcen.uba.ar.
E1A is the main transforming protein in mastadenoviruses. This work uses bioinformatics to extrapolate experimental knowledge from Human adenovirus serotype 5 and 12 E1A proteins to all known serotypes. A conserved domain architecture with a high degree of intrinsic disorder acts as a scaffold for multiple linear motifs with variable occurrence mediating the interaction with over fifty host proteins. While linear motifs contribute strongly to sequence conservation within intrinsically disordered E1A regions, motif repertoires can deviate significantly from those found in prototypical serotypes. Close to one hundred predicted residue-residue contacts suggest the presence of stable structure in the CR3 domain and of specific conformational ensembles involving both short- and long-range intramolecular interactions. Our computational results suggest that E1A sequence conservation and co-evolution reflect the evolutionary pressure to maintain a mainly disordered, yet non-random conformation harboring a high number of binding motifs that mediate viral hijacking of the cell machinery.
Virology 525: 117-131 (2018)