Protein kinase A targeting and activation as seen by small-angle solution scattering.

We have studied the solution structures of the multi-functional protein kinase A using small-angle X-ray and neutron scattering and have found a remarkable structural diversity in the different isoforms of this multi-subunit enzyme, in spite of its having high sequence homology and a common domain organization within its sequences. The available high-resolution crystal and NMR structural data for the protein kinase A components have aided in the interpretation of the solution scattering data and enabled us to develop models that bring insights into protein kinase A activation and targeting mechanisms, such as the opening and closing of the catalytic cleft to facilitate substrate binding or inhibition, respectively, and the role of sequence segments that join functional domains in the R subunit in providing a structurally flexible scaffold for interactions with the C subunit and A kinase-anchoring proteins (AKAPs).