Abstract
Over the last few decades, concepts of protein intrinsic disorder have been implicated in different biological processes. Recent studies have suggested that intrinsically disordered proteins (IDPs) provide structural plasticity and functional diversity to viral proteins that are involved in rapid replication and immune evasion in host cells. In case of Zika virus, the roles of protein intrinsic disorder in mechanisms of pathogenesis are not completely understood. In this study, we have analyzed the prevalence of intrinsic disorder in Zika virus proteome (strain MR 766). Our analyses revealed that Zika virus polyprotein is enriched with intrinsically disordered protein regions (IDPRs) and this finding is consistent with previous reports on the involvement of IDPs in shell formation and virulence of the Flaviviridae family. We found abundant IDPRs in Capsid, NS2B, NS3, NS4A, and NS5 proteins that are involved in mature particle formation and replication. In our view, the intrinsic disorder-focused analysis of ZIKV proteins could be important for the development of disorder-based drugs.
Highlights
In 1947, Zika virus (ZIKV) was first identified in Uganda through a monitoring network of sylvatic yellow fever in rhesus monkeys (Dick et al, 1952)
IUPred was designed to recognize intrinsically disordered protein regions (IDPRs) from the amino acid sequence alone based on the estimated pairwise energy content, where it was hypothesized that globular proteins are composed of amino acids which have the potential to form a large number of favorable interactions, whereas intrinsically disordered proteins (IDPs)/IDPRs do not have unique 3D structure because their amino acid composition does not allow sufficient favorable interactions to form (Dosztanyi et al, 2005a,b)
Despite obvious interest to Zika virus, crystallographic data are currently available only for four ZIKV proteins, NS1, NS2B-NS3 protease (residues 49 to 95 of NS2B covalently linked via Gly4-Ser-Gly4 to the N-terminal protease domain of NS3), NS3, M and E proteins
Summary
In 1947, Zika virus (ZIKV) was first identified in Uganda through a monitoring network of sylvatic yellow fever in rhesus monkeys (Dick et al, 1952). Distribution of Zika infection is mainly associated with the distribution of Aedes mosquito vectors that can be found in different parts of the world (Wikan and Smith, 2016). A recent study on immunocompetent mouse model has strengthened the previous observations that ZIKV infection might cause neurological defects in fetuses (Lazear et al, 2016). This virus is transmitted through mosquitos, as well as via blood transfusion and from mother to fetus during pregnancy (Wikan and Smith, 2016). Reports suggest the possibility of sexual transmission (Grischott et al, 2016)
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