RNA-induced Allosteric Coupling Drives Viral Capsid Assembly.

Understanding the mechanisms by which single-stranded RNA viruses regulate capsid assembly around their RNA genomes has become increasingly important for the development of both antiviral treatments and drug delivery systems. In this study, we investigate the effects of RNA-induced allostery in a single-stranded RNA virus-Levivirus bacteriophage MS2 assembly-using the computational methods of the Dynamic Flexibility Index and the Dynamic Coupling Index. We demonstrate that not only does asymmetric binding of RNA to a symmetric MS2 coat protein dimer increase the flexibility of the distant FG-loop, inducing a conformational change to an asymmetric dimer, but also RNA binding reorganizes long-distance communications, making all the other positions extremely sensitive to the fluctuation of the ordered FG-loop. Additionally, we find that a point mutation in the FG-loop, W82R, leads to the loss of this asymmetry in communications, likely being a leading cause for assembly-deficient dimers. Lastly, this dominant communication that enhances its dynamic coupling with all the distal positions is not only a property of the dimer but is also exhibited by all the observed capsid intermediates. This strong dynamic coupling allows for unidirectional signal transduction that drives the formation of the experimentally observed capsid intermediates and fully assembled capsid.