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Full-Text Articles in Biochemistry
Intrinsic Disorder Within An Akap-Protein Kinase A Complex Guides Local Substrate Phosphorylation, F. Donelson Smith, Steve L. Reichow, Jessica L. Esseltine, Dan Shi, Lorene K. Langeberg, John D. Scott, Tamir Gonen
Intrinsic Disorder Within An Akap-Protein Kinase A Complex Guides Local Substrate Phosphorylation, F. Donelson Smith, Steve L. Reichow, Jessica L. Esseltine, Dan Shi, Lorene K. Langeberg, John D. Scott, Tamir Gonen
Chemistry Faculty Publications and Presentations
Anchoring proteins sequester kinases with their substrates to locally disseminate intracellular signals and avert indiscriminate transmission of these responses throughout the cell. Mechanistic understanding of this process is hampered by limited structural information on these macromolecular complexes. A-kinase anchoring proteins (AKAPs) spatially constrain phosphorylation by cAMP-dependent protein kinases (PKA). Electron microscopy and three-dimensional reconstructions of type-II PKA-AKAP18γ complexes reveal hetero-pentameric assemblies that adopt a range of flexible tripartite configurations. Intrinsically disordered regions within each PKA regulatory subunit impart the molecular plasticity that affords an ∼16 nanometer radius of motion to the associated catalytic subunits. Manipulating flexibility within the PKA holoenzyme …