The allosteric switching mechanism in bacteriophage MS2

Area of Science:

• Structural Biology
• Biophysics
• Virology

Background:

• Icosahedral virus capsid assembly requires precise conformational states of capsid proteins.
• The MS2 bacteriophage coat protein undergoes conformational switching during assembly.
• A 19-nucleotide stem loop (TR) from the MS2 genome acts as an allosteric effector for coat protein assembly.

Purpose of the Study:

• To elucidate the molecular mechanisms of conformational switching and allostery in the MS2 bacteriophage coat protein.
• To understand how TR RNA binding allosterically communicates with distant sites on the coat protein.
• To identify the role of specific amino acid networks in mediating allosteric effects.

Main Methods:

• All-atom simulations with explicit water.
• Path sampling techniques to study conformational transitions.
• Analysis of molecular interactions and correlated motions.

Main Results:

• TR RNA binding significantly alters the free energy profile of coat protein conformational transitions, favoring specific conformations.
• TR binding impacts molecular interactions, driving conformational shifts.
• Networks of amino acids with correlated motions were identified, explaining the long-range effects of TR binding.
• TR binding affects residues at the 5-fold and quasi-sixfold interfaces, potentially directing native capsid geometry formation.

Conclusions:

• All-atom simulations reveal the molecular basis of RNA-mediated allosteric control in MS2 virus assembly.
• The findings provide insights into how RNA ligands can direct protein conformational changes and assembly pathways.
• The study predicts specific amino acid residues whose mutagenesis could modulate coat protein conformational dynamics.