Abstract : Signatures of environmental adaptation of allostery in protein homologues.
Allosteric proteins exploit dynamics and conformational changes to effectively couple distant sites responsible for the initial activation and catalysis. To date, research effort has routinely focused on studying ligand binding to the functional sites of proteins (active sites of enzymes), whereas the molecular mechanisms of allosteric regulation remains poorly understood. In particular, little is known on wether proteins from different organisms, absolving for the same function adapt their allosteric pathways and how. Therefore, understanding how allosteric enzymes from different evolutionary paths achieve the same catalytic function remains a subject of great fundamental interest. Here, we examine the allosteric pathways of the imidazole glycerol phosphate synthase (IGPS) enzymes from yeast and thermophilic bacteria by combining molecular dynamics simulations and network models derived from graph theory. We find rather distinct allosteric pathways in the two enzymes from different evolutionary paths although with the same function, involving cooperative interactions between local and collective modes. Bacterial IGPS exhibits an allosteric mechanism that involves a hinge-like motion at the cyclase:glutaminase interface of the HisF and HisH enzyme subunits. In contrast, IGPS from yeast exhibits a spring-like motion with protein expansion and contraction mediating a more direct and internal allosteric pathway. Remarkably, the two rather different mechanisms accomplish the same function of activating the catalytic site upon effector binding to the allosteric site.
- This évènement has passed.
