Intrinsic Disorder Contribution to Open Reading Frame 4: Implications in Regulation & Pathogenesis of HEV

Due to insufficiency in appropriate hepatitis E virus (HEV) in vitro cell culture systems, our knowledge of its pathogenesis is inadequately understood. Viral proteins entail disordered regions that are linked with the infectivity and pathogenicity of the virus. Despite the general belief that unique biological functions of proteins require unique 3D structures (which dominated protein science for more than a century), structure-less intrinsically disordered proteins (IDPs)/intrinsically disordered protein regions (IDPRs) are functional, being able to engage in biological activities and perform impossible tricks that are highly unlikely for ordered proteins. The distribution of intrinsically disordered regions (IDRs) in the ORF4 protein is of great importance in the regulation of HEV. Thus, we examined the unstructured regions (IDRs) of this additional reading frame encoded protein ORF4, completely embedded inside ORF1, by analysing its IDRs, by exploiting computational methodologies. Our findings suggested that ORF4 had the prevalence of disordered regions. IDPRs are characterized by remarkable conformational flexibility and structural plasticity resulting in their engagement in several biological processes. In this chapter, some wonders of intrinsic disorder contribution to ORF4’s functions have been discussed.