The functional regulatory details of ERK2 in complex with RSK1: an insight.

Protein kinases play a significant role in cellular activation procedures by exhibiting a vivid selection in the target, as well as recognizing and phosphorylating them. Extracellular signal-regulated kinase 2 (ERK2) is one of the main kinases in the mitogen-activated protein kinase (MAPK) signaling cascade and engages in dynamically regulating the activities of signaling proteins and physiological processes, including cell proliferation, differentiation, adhesion, migration, and survival. Predicting collective dynamic and structural motions in biological macromolecules is pivotal to obtain a better understanding of the majority of biological processes. Here, through molecular dynamic simulation and normal mode analysis, we investigated ERK2 conformations, in the forms of active (phosphorylated), inactive (unphosphorylated), and in a complex with its substrate, ribosomal protein S6 kinase alpha-1 (RSK1), to determine functional characteristics. Our finding demonstrated that ERK2 plays a switch role in the regulation of pathways. In the case that this protein kinase is in the active form, all critical regions shift to be prepared to accept the substrate and catalytic action. Meanwhile, inactive ERK2 shows contrasting results in which all motions tend to close the catalytic site and cease the phosphorylation action in the MAPK cascade. These findings are in line with those from other similar studies and provide us with novel molecular target regions and recent details on how this mechanism works.