Interplay between sequence, structure and linear motifs in the adenovirus E1A hub protein.

Juliana Glavina, Ernesto A Román, Rocío Espada, Gonzalo de Prat-Gay, Lucía B Chemes, Ignacio E Sánchez

Journal: Virology 2019;525():117-131

PMID: 30265888

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Abstract

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.

Address: Universidad de Buenos Aires. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN). Facultad de Ciencias Exactas y Naturales. Laboratorio de Fisiología de Proteínas. Buenos Aires, Argentina.; Instituto de Química y Físico-Química Biológicas, Universidad de Buenos Aires, Junín 956, 1113AAD, Buenos Aires, Argentina.; Protein Structure-Function and Engineering Laboratory, Fundación Instituto Leloir and IIBBA-CONICET, Buenos Aires, Argentina.; Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Biotecnológicas IIB-INTECH, Universidad Nacional de San Martín, San Martín, Buenos Aires, Argentina; Departamento de Fisiología y Biología Molecular y Celular (DFBMC), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina. Electronic address: [email protected].; Universidad de Buenos Aires. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN). Facultad de Ciencias Exactas y Naturales. Laboratorio de Fisiología de Proteínas. Buenos Aires, Argentina. Electronic address: [email protected].

DOI: 10.1016/j.virol.2018.08.012

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MeSH Terms: Adenovirus E1A Proteins, Adenoviruses, Human, Amino Acid Motifs, Amino Acid Sequence, Humans, Protein Conformation, Protein Domains, Protein Modification, Translational