3J4Q
Pseudo-atomic model of the AKAP18-PKA complex in a bent conformation derived from electron microscopy
Summary for 3J4Q
| Entry DOI | 10.2210/pdb3j4q/pdb |
| Related | 3J4R |
| EMDB information | 5755 5756 |
| Descriptor | A-kinase anchor protein 18, cAMP-dependent protein kinase type II-alpha regulatory subunit, cAMP-dependent protein kinase catalytic subunit alpha (3 entities in total) |
| Functional Keywords | a-kinase anchoring protein, camp-dependent kinase, rii, pka regulatory subunit ii, phosphorylation, anchoring, intrinsic disorder, transferase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 212024.42 |
| Authors | Reichow, S.L.,Gonen, T. (deposition date: 2013-09-25, release date: 2013-11-13, Last modification date: 2024-02-21) |
| Primary citation | Smith, F.D.,Reichow, S.L.,Esseltine, J.L.,Shi, D.,Langeberg, L.K.,Scott, J.D.,Gonen, T. Intrinsic disorder within an AKAP-protein kinase A complex guides local substrate phosphorylation. Elife, 2:e01319-e01319, 2013 Cited by PubMed Abstract: 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 augmented basal and cAMP responsive phosphorylation of AKAP-associated substrates. Cell-based analyses suggest that the catalytic subunit remains within type-II PKA-AKAP18γ complexes upon cAMP elevation. We propose that the dynamic movement of kinase sub-structures, in concert with the static AKAP-regulatory subunit interface, generates a solid-state signaling microenvironment for substrate phosphorylation. DOI: http://dx.doi.org/10.7554/eLife.01319.001. PubMed: 24192038DOI: 10.7554/eLife.01319 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (35 Å) |
Structure validation
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