Structural disorder within the measles virus nucleoprotein and phosphoprotein

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• Measles virus (MeV) nucleoprotein (N) and phosphoprotein (P) are known to possess significant structural disorder.
• Intrinsically disordered regions in viral proteins play critical roles in molecular interactions and biological functions.

Purpose of the Study:

• To review experimental data on structural disorder in MeV N and P proteins.
• To elucidate the molecular mechanisms of disorder-to-order transitions in the MeV N C-terminal domain (N(TAIL)) upon binding to the P C-terminal X domain (XD).
• To discuss the functional implications of protein disorder in MeV, including interactions with cellular co-factors.

Main Methods:

• Review of existing experimental data on MeV protein structure and function.
• Analysis of molecular mechanisms governing protein-protein interactions and disorder-to-order transitions.
• Discussion of the role of intrinsically disordered regions in viral processes.

Main Results:

• Structural disorder is abundant in MeV nucleoprotein (N) and phosphoprotein (P).
• The N(TAIL) domain transitions from a disordered to an ordered state upon binding to the P XD domain.
• Disordered regions facilitate complex molecular partnerships, influencing viral polymerase complex tethering, transcription, replication, and assembly.
• N(TAIL) interacts with cellular co-factors like heat shock proteins, modulating N(TAIL)-XD interactions.

Conclusions:

• Protein structural disorder in MeV contributes to pleiotropy and genetic economy.
• Disordered regions enable single viral genes to encode multifunctional proteins, mediating multiple biological effects.
• The ability of disordered regions to engage in multiple interactions is a key functional advantage for viruses.