Studying The Role Of Protein Flexibility In Allosteric And Evolutionary Changes As Seen In Pyrr Protein Family

Oligomerisation is essential for the function of some proteins. The PyrR family of proteins are involved in pyrimidine operon attenuation. They are regulated by the presence of certain nucleotides such as guanosine monophosphate (GMP), which stabilises the tetrameric state. Notably, some members of this family can adopt a tetrameric oligomerisation state regardless of the presence of the GMP. Perica et al. (2012) previously found that this family, among several others, have differences in sequence outside the oligomeric interfaces and these are sufficient to explain the changes to their subunit geometry and oligomerisation states. Here, we compared the differences in structural flexibility linked to the changes in oligomeric state caused by a) specific mutations and, b) by the presence of bound GMP. We calculated the coarse-grained normal modes of dimeric units of the PyrR dimers and tetramers using an Elastic Network Model implemented in the Molecular Modelling ToolKit. We conducted several analyses including comparing the normal modes of these proteins with each other using the Bhattacharyya Coefficient similarity measure, correlations matrices, and the conformational overlap analysis, by which the contribution of these modes to the transition from one state to another can be quantified. Firstly, we found that while the dynamics were very similar between all the structures, there was a noticeable difference between the dimeric and tetrameric units. We also show that both sets of proteins transition from tetrameric to dimeric states similarly, indicating some overlap between the effects of allostery and evolution on oligomerisation in PyrR.