Japanese encephalitis virus - exploring the dark proteome and disorder-function paradigm.

Area of Science:

• Virology
• Structural Biology
• Bioinformatics

Background:

• Japanese encephalitis virus (JEV) causes significant global viral encephalitis, posing a risk to 3 billion people.
• Understanding the JEV proteome, including disordered proteins, is crucial for a holistic view.
• The role of intrinsically disordered regions in JEV has not been systematically studied.

Purpose of the Study:

• To systematically analyze the JEV proteome for intrinsic disorder and disorder-based binding regions (MoRFs).
• To identify potential nucleic acid-binding sites within JEV proteins.
• To experimentally validate bioinformatic findings using the JEV capsid protein.

Main Methods:

• Bioinformatic analysis of the JEV proteome using specialized tools.
• Prediction of intrinsically disordered regions and MoRFs.
• Experimental validation including temperature response assays, gain-of-structure potential, and liposome interaction studies.

Main Results:

• Bioinformatic analysis revealed intrinsic disorder and potential nucleic acid-binding sites in JEV proteins.
• The N-terminal region (residues 1-30) of the JEV capsid protein was confirmed as intrinsically disordered.
• Experimental studies showed temperature-dependent behavior, 'gain-of-structure' potential, and membrane-mediated conformational changes in the JEV capsid's disordered region.

Conclusions:

• Intrinsic disorder plays a significant role in the JEV proteome.
• The disordered N-terminal domain of the JEV capsid protein exhibits functional flexibility and membrane interactions.
• Disorder-centric analysis offers valuable insights into JEV pathogenesis.