Protein phosphorylation plays an important role in many cellular processes, now researchers in the Phosphoprocessors project aim to learn more about the molecular basis of this process. This work could have important implications for the design of circuits for synthetic biology, as Professor Mart Loog explains
Analysing the basis of protein phosphorylation Protein phosphorylation by
protein kinases plays a central role in many cellular processes. The addition of a negatively charged phosphoryl group can change the function of a protein, which then may lead on to further changes. “If you add another phosphate group to the protein, you can activate the protein or de-activate it, or localise it to other parts of the cell,” explains Professor Mart Loog, the Principal Investigator of the Phosphoprocessors project. Researchers in the project now aim to learn more about multisite phosphorylation, looking in particular towards three main objectives. “One is related to the regulation of cell division, and regulation of temporal order of individual molecular events in cell cycle and cell division,” outlines Professor Loog. “We’re looking at how the master regulators of this process, cyclindependent kinases (CDK), are able to
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temporarily resolve these triggers and switches and other molecular events.” A second key objective in the project is to study the phosphorylation of proteins in kinetochores, a type of large protein structure. The main topic of interest here is the regulation of protein function through phosphorylation; the enzymes which catalyse this are protein kinases. “We are focusing on CDKs, as master regulators of the cell cycle. So far, we have studied this process with respect to individual substrate proteins, but now we are going to study it in the context of larger protein structures. We expect that we will find different rules and dynamics, as this is a new area of research,” says Professor Loog. The third objective is related to synthetic biology, synthetic circuit design.“We aim to apply the knowledge that we have gained from studying multi-site phosphorylation circuits in the cell
cycle – we aim to apply the same rules in designing regulatory circuits, in synthetic cellular systems,” continues Professor Loog.
Multi-site phosphorylation This work builds on continued research into the phosphorylation process. Within the project, researchers are looking in particular at multisite phosphorylation, in which the phosphoryl groups are attached at different sites in the proteins. “These sites can be distributed within the peptide chain in different patterns and clusters, with different distances between them, and different amino acids around them. These are the parameters that define the phosphorylation process – the kinetics of it, the dynamics of it, and basically, how its inputs and outputs are controlled,” explains Professor Loog. The aim in the project is to crack the ‘multisite phosphorylation code’ of CDK, while
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