Intrinsically disordered proteins of viruses: Involvement in the mechanism of cell regulation and pathogenesis

Abstract

Intrinsically disordered proteins (IDPs) possess the property of inherent flexibility and can be distinguished from other proteins in terms of lack of any fixed structure. Such dynamic behavior of IDPs earned the name "Dancing Proteins." The exploration of these dancing proteins in viruses has just started and crucial details such as correlation of rapid evolution, high rate of mutation and accumulation of disordered contents in viral proteome at least understood partially. In order to gain a complete understanding of this correlation, there is a need to decipher the complexity of viral mediated cell hijacking and pathogenesis in the host organism. Further there is necessity to identify the specific patterns within viral and host IDPs such as aggregation; Molecular recognition features (MoRFs) and their association to virulence, host range and rate of evolution of viruses in order to tackle the viral-mediated diseases. The current book chapter summarizes the aforementioned details and suggests the novel opportunities for further research of IDPs senses in viruses.

Keywords: Aggregation; Cell hijacking; Dancing proteins; IDPs; MoRFs; Viruses.

Fig. 1

IDPs involvement in various cellular processes.,

Fig. 2

Intrinsic disorder controlled (A) a structural change in the cyclin-dependent kinase inhibitor 1B (p27^Kip1); (B) TADp53-mediated Mdm2 binding have an association with the cell cycle regulation and apoptosis. (C) Conformational fluctuation and transient exposure of interaction motif lead to PTM that subsequently controls the target binding and ultimately regulation of cell cycle. (D) IDRs control zinc-binding domain of EMI-1 that upon interaction with APC/C complex controls UBQ-mediated degradation of cyclins and other proteins that are related to the cell cycle regulation. (E) Viruses hijack the cellular machinery using one or more cell regulation pathways by using their proteins to mimic the host IDPs/IDRs in cell cycle pathways.

Fig. 3

Host cell cycle regulation influenced by the attack of viral protein components on pRb and E2F complex. Viral protein complex forcibly releases the E2F from pRb and E2F complex and abruptly increases the cell cycle progression in an uncontrolled way. The blue color shows the normal pathway of G1 to S progression, while red color shows virus-induced uncontrolled cell progression from G1 to S.

Fig. 4

Comparative analysis of IDPs contents to intrinsic aggregation (and Intrinsic solubility) propensity in three viruses genome polyprotein; JEV (UniProt id: P27395), EV-71 (UniProt id: Q66478) and ZIKV (UniProt id: A0A024B7W1) that impacted India). A, C, E represents IDPs content (and MoRF) propensity in JEV, EV-71, and ZIKV respectively determined by IUPred2A while B, D, F show Aggregation propensity (and Intrinsic solubility) in JEV, EV-71 and ZIKV respectively determined by CamSol method Vendruscolo lab software., A relation between IDPs content and aggregation propensity and viral infection pattern could be established.

Fig. 5

The capsid protein MoRF position (toggled gray bars) predicted by the MoRFchibi system for (A) ZIKV (UniProt id: Q32ZE1| 1-104); (B) DENV (UniProt id: P33478| 1-100). Three MoRF regions of different lengths have observed in the capsid protein of both viruses, located within disordered areas, these MoRF regions play a crucial role by recognizing, interacting and inducing a conformational change to viral as well as host proteins.

Fig. 6

Intrinsic disorder prediction in TGB1 protein (Uniprot Id: P04867) of Barley stripe mosaic virus by IUpred2A server.