Susan Taylor

Structure, Function, Dynamics, and Localization of PKA as a Prototype for the Protein Kinase Superfamily

Our primary focus is to understand the structure, function and dynamics of cAMP-dependent protein kinase (PKA) using biochemical, biophysical and recombinant approaches. The catalytic (C) subunit was the first protein kinase structure to be solved and continues to serve as a prototype for all protein kinases, now recognized as one of the largest gene superfamilies. In parallel with crystallography, kinetics, fluorescence, H/D exchange, and small angle Xray/neutron scattering are used to define conformational changes, ligand binding sites, and sites of protein:protein interaction.

Structures of RIa and RIIß regulatory subunits reveal critical isoform-specific differences. Most recently holoenzyme complexes were solved for RIa, RIIa, and RIIß, and these reveal major conformational changes in the R subunits as they release cAMP and bind to the C subunit. Based on SAXS, the architecture of the holoenzymes differ significantly. The dimerization domain at the R-subunit N-terminus serves as a docking site for A Kinase Anchoring Proteins (AKAPs). Structures of the D/D domains for RIa and RIIa were solved by NMR and by crystallography, respectively.

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