Summary for 9EDD
| Entry DOI | 10.2210/pdb9edd/pdb |
| Related | 9EDC |
| EMDB information | 47944 47945 |
| Descriptor | cAMP-dependent protein kinase catalytic subunit alpha, cAMP-dependent protein kinase type I-alpha regulatory subunit, ADENOSINE-5'-TRIPHOSPHATE (3 entities in total) |
| Functional Keywords | kinase, regulator, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 88622.97 |
| Authors | Venkatakrishnan, V.,Buckley, T.,Laremore, T.N.,Armache, J.P.,Anand, G.S. (deposition date: 2024-11-16, release date: 2025-04-23, Last modification date: 2025-05-14) |
| Primary citation | Venkatakrishnan, V.,Laremore, T.N.,Buckley, T.S.C.,Armache, J.P.,Anand, G.S. Multiplicity of Regulatory Subunit Conformations Defines Structural Ensemble of Reset Protein Kinase A Holoenzyme. J.Am.Chem.Soc., 147:14174-14190, 2025 Cited by PubMed Abstract: How protein kinase A (PKA) is reset to a basal state following 3'5'-cyclic adenosine monophosphate (cAMP)-mediated activation is unknown. Here we describe the mechanism of cAMP-PKA type I signal termination leading to a reset of PKA by holoenzyme formation through the obligatory action of phosphodiesterases (PDEs). We report a catalytic subunit (Cα)-assisted mechanism for the reset of type I PKA and describe for the first time multiple structures of the reset PKA holoenzyme (RIα:Cα) that capture an ensemble of multiple conformational end-states through integrative electron microscopy and structural mass spectrometry approaches. Together these complementary methods highlight the large conformational dynamics of the regulatory subunit (RIα) within the tetrameric reset PKA holoenzyme. The cAMP-free reset PKA holoenzyme adopts multiple distinct conformations of RIα with contributions from the N-terminal linker and CNB-B dynamics. Our findings highlight the interplay between RIα, Cα, and PDEs (PDE8) in cAMP-PKA signalosomes to offer a new paradigm for PDE-mediated regulation of cAMP-PKA signaling. PubMed: 40241376DOI: 10.1021/jacs.4c16269 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (6.3 Å) |
Structure validation
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