tailieunhanh - Báo cáo Y học: Electrostatic properties of the structure of the docking and dimerization domain of protein kinase A IIa

The structure of the N-terminal docking and dimerization domain of the type IIa regulatory subunit (RIIa D/D) of protein kinase A (PKA) forms a noncovalent stand-alone X-type four-helix bundle structural motif, consisting of two helix-loop-helix monomers. RIIa D/D possesses a strong hydrophobic core and two distinct, exposed faces. A hydrophobic face with a groove is the site of protein–protein interactions necessary for subcellular localization. | Eur. J. Biochem. 269 2040-2051 2002 FEBS 2002 doi Electrostatic properties of the structure of the docking and dimerization domain of protein kinase A IIa Dimitrios Morikis1 Melinda Roy2 Marceen G. Newlon2 John D. Scott3 and Patricia A. Jennings2 1 Department of Chemical and Environmental Engineering University of California at Riverside Riverside USA 2Department of Chemistry and Biochemistry University of California at San Diego La Jolla USA 3Howard Hughes Medical Institute Vollum Institute Portland OR USA The structure of the N-terminal docking and dimerization domain of the type IIa regulatory subunit RIIa D D of protein kinase A PKA forms a noncovalent stand-alone X-type four-helix bundle structural motif consisting of two helix-loop-helix monomers. RIIa D D possesses a strong hydrophobic core and two distinct exposed faces. A hydrophobic face with a groove is the site of protein-protein interactions necessary for subcellular localization. A highly charged face opposite to the former may be involved in regulation of protein-protein interactions as a result of changes in phosphorylation state of the regulatory subunit. Although recent studies have addressed the hydrophobic character of packing of RIIa D D and revealed the function of the hydrophobic face as the binding site to A-kinase anchoring proteins AKAPs little attention has been paid to the charges involved in structure and function. To examine the electrostatic character of the structure of RIIa D D we have predicted mean apparent pKa values based on Poisson-Boltzmann electrostatic calculations using an ensemble of calculated dimer structures. We propose that the helix promoting sequence Glu34-X-X-X-Arg38 stabilizes the second helix of each monomer through the formation of a i i 4 side chain salt bridge. We show that a weak interhelical hydrogen bond between Tyr35-Glu19 of each monomer contributes to tertiary packing and may be responsible for discriminating from .