Intrinsic disorder in protein kinase A anchoring proteins signaling complexes
| Autor: | Mateusz Dyla, Magnus Kjaergaard |
|---|---|
| Přispěvatelé: | Uversky, Vladimir N. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Scaffold protein
chemistry.chemical_classification Scaffolding protein Chemistry Effective concentration Protein subunit Intrinsically disordered region Allosteric regulation Phosphatase Tethered catalysis Substrate (chemistry) A kinase anchoring protein (AKAP) Enzyme Disordered linker Biophysics Cyclic AMP Phosphorylation Protein kinase A (PKA) Protein kinase A |
| Zdroj: | Dyla, M & Kjaergaard, M 2021, Intrinsic disorder in protein kinase A anchoring proteins signaling complexes . in V N Uversky & V N Uversky (eds), Dancing Protein Clouds : Intrinsically Disordered Proteins in the Norm and Pathology, Part C . Elsevier, Amsterdam, Progress in Molecular Biology and Translational Science, vol. 183, pp. 271-294 . https://doi.org/10.1016/bs.pmbts.2021.06.005 Progress in Molecular Biology and Translational Science ISBN: 9780323852999 |
| DOI: | 10.1016/bs.pmbts.2021.06.005 |
| Popis: | Protein kinase A (PKA) is regulated by a diverse class of anchoring proteins known as AKAPs that target PKA to subsets of its activators and substrates. Recently, it was reported that PKA can remain bound to its regulatory subunit after activation in contrast to classical model of activation-by-dissociation. This implies that PKA remains bound to the AKAPs and its substrates, and thus suggest many phosphorylation reactions occur while PKA is physically connected to its substrate. Intra-complex reactions are sensitive to the architecture of the signaling complex, but generally concentration independent. We show that most AKAPs have long intrinsically disordered regions, and suggest that they represent an adaptation for intra-complex phosphorylation. Based on polymer models of the disordered proteins, we predict that the effective concentrations of tethered substrates range from the low millimolar range to tens of micromolar. Based on recent models for intra-complex enzyme reactions, we suggest that the structure of the AKAP signaling complex is likely to be source of allosteric regulation of PKA signaling. |
| Databáze: | OpenAIRE |
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