Conservation of Sequence, Structure and Linear Motifs within the intrinsically disordered and globular domains of the adenovirus E1A oncoprotein

JULIANA GLAVINA; IGNACIO SANCHEZ; ROCIO ESPADA; ERNESTO A. ROMAN; LUCIA CHEMES; GONZALO DE PRAT-GAY

Ciudad Autonoma de Buenos Aires

Congreso; ISCB Latin America 2016; 2016

ISCB

Background: Viruses manipulate the host cell cycle through interaction with key host proteins. Many of these interactions are mediated by linear motifs of 5 to 15 function-determining residues, often found within intrinsically disordered domains. The Adenovirus E1A protein mediates cell transformation in several animals and consists of 5 previously defined regions: N-Domain, CR1, CR2, CR3 and CR4.Results: We used an alignment of 116 sequences to study conservation of sequence, structure and function in E1A. The IUPRED algorithm indicates that CR1, CR2, and CR4 are disordered, while a region within CR3 is globular. The sequence of these three disordered domains is as conserved as that of the globular domain. The disordered domains of E1A are densely packed with 11 linear motifs that explain the high number of binding partners and show varying degrees of prevalence (6 to 97%). Motif-determining positions are more conserved than wildcard motif positions and than positions elsewhere in the protein. Residue contacts in E1A predicted using direct information suggest that this mainly disordered protein does not behave as a constraint-free entropic chain. Contact predictions within CR3 were used to build a structural model for the domain, which should help understand its function.Conclusions: Sequence conservation of E1A disordered regions is as high as in structured regions. However, the cause is different: Disordered regions contain multiple motifs while CR3 conservation can be mainly ascribed to structure conservation. E1A shows a well defined structural motif within CR3 and a looser three-dimensional organization that involves all disordered regions.