Protein kinase A (PKA) is involved in many cellular events and its activity can be tweaked and compartmentalized through mirystoylation of its N-terminus. (Mirystoylation is a type of protein modification that plays a role in directing and anchoring proteins to membranes and, thus, is involved with cellular regulation, signal transduction, and apoptosis.)
Research Associate Dr. Alessandro Cembran, who works with MSI PIs Professor Gianluigi Veglia (Biochemistry, Molecular Biology, and Biophysics) and Professor Jiali Gao (MSI Fellow, Chemistry), presented a poster at the 2012 MSI Research Exhibition about research he, Professors Veglia and Gao, and Research Associate Dr. Larry Masterson performed concerning PKA. The PKA catalytic subunit (PKA-C) mediates the transfer of the γ-phosphate group from ATP to threonine or serine residues. PKA activity must be tightly controlled in time and space, and myristoylation of its N-terminus is a regulatory mechanism that is not yet fully understood. The research presented in the poster investigated the short- and long-range structural and dynamical effects of PKA-C N-myristoylation through a combined experimental and computational approach. The group uses MSI resources to perform structural modeling and molecular dynamics simulations of cardiac proteins in their native lipid environment.
The results showed that myristoylation induces changes in structure and dynamics of the residues surrounding the myristoyl group, as well as long range perturbations involving catalytically relevant residues.
The image above shows the structure of the myristoylated kinase. Highlighted in the box is the allosteric link, responsible for the transmission of the allosteric signal from the myristoyl group to the active site. On the right, distance matrix analysis allows to identify regions in close contact.