RNA-induced allosteric coupling drives viral capsid assembly in the single-stranded RNA virus bacteriophage MS2.

Abstract

Single-stranded RNA viruses are the simplest viruses and are known to infect every domain of life. Consequently, understanding the mechanisms by which RNA regulates capsid assembly has become increasingly important for the development of both antiviral treatments and drug delivery systems. Here, we investigate the effects of RNA-induced allostery in a single-stranded RNA virus --- Levivirus bacteriophage MS2 --- using the computational methods of the Dynamic Flexibility Index (DFI) and the Dynamic Coupling Index (DCI). We show that asymmetric binding of RNA to a symmetric MS2 coat protein dimer increases the flexibility of the distant FG-loop (residues 68-82) and induces a conformational change to an asymmetric dimer that is essential for proper capsid formation. We also show that a point mutation W82R in the FG-loop creates an assembly-deficient dimer in which RNA-binding has no significant effect on FG-loop flexibility. Lastly, we provide evidence for the existence of an allosteric coupling mechanism that also drives the formation of the experimentally observed capsid intermediates.