ArticleThe Journal of biological chemistry2010
Communication between tandem cAMP binding domains in the regulatory subunit of protein kinase A-Ialpha as revealed by domain-silencing mutations.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- Recurrent Acrodysostosis-Related PKA RIα Mutant Reveals a Novel Mechanism of Aberrant PKA Deactivation.Journal of molecular biology · 2025Article
- Interaction networks explain holoenzyme allostery in Protein Kinase A.Kinases and phosphatases · 2023Article
- Conformational changes in protein kinase A along its activation cycle are rooted in the folding energetics of cyclic-nucleotide binding domains.The Journal of biological chemistry · 2023Article
- Mutation-Induced Long-Range Allosteric Interactions in the Spike Protein Determine the Infectivity of SARS-CoV-2 Emerging Variants.ACS omega · 2021Article
- State-selective frustration as a key driver of allosteric pluripotency.Chemical science · 2021Article
- Noncanonical protein kinase A activation by oligomerization of regulatory subunits as revealed by inherited Carney complex mutations.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- Allosteric Mechanisms of Nonadditive Substituent Contributions to Protein-Ligand Binding.Biophysical journal · 2020Article
- Mechanism of allosteric inhibition in theThe Journal of biological chemistry · 2020Article
- Allosteric pluripotency as revealed by protein kinase A.Science advances · 2020Article
- Exploring the structural basis of conformational heterogeneity and autoinhibition of human cGMP-specific protein kinase Iα through computational modelling and molecular dynamics simulations.Computational and structural biotechnology journal · 2020Article
- Review
- Two PKA RIα holoenzyme states define ATP as an isoform-specific orthosteric inhibitor that competes with the allosteric activator, cAMP.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Switching of the folding-energy landscape governs the allosteric activation of protein kinase A.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Unidirectional allostery in the regulatory subunit RIα facilitates efficient deactivation of protein kinase A.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Protein Allostery and Conformational Dynamics.Chemical reviews · 2016Review
- Parallel Allostery by cAMP and PDE Coordinates Activation and Termination Phases in cAMP Signaling.Biophysical journal · 2015Article
- Role of Dynamics in the Autoinhibition and Activation of the Hyperpolarization-activated Cyclic Nucleotide-modulated (HCN) Ion Channels.The Journal of biological chemistry · 2015Article
- Mapping the Hydrogen Bond Networks in the Catalytic Subunit of Protein Kinase A Using H/D Fractionation Factors.Biochemistry · 2015Article
- Mapping the Free Energy Landscape of PKA Inhibition and Activation: A Double-Conformational Selection Model for the Tandem cAMP-Binding Domains of PKA RIα.PLoS biology · 2015Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Protein kinase A (PKA) is the main receptor for the universal cAMP second messenger. PKA is a tetramer with two catalytic (C) and two regulatory (R) subunits, each including two tandem cAMP binding domains, i.e. CBD-A and -B. Structural investigations of RIalpha have revealed that although CBD-A plays a pivotal role in the cAMP-dependent inhibition of C, the main function of CBD-B is to regulate the access of cAMP to site A. To further understand the mechanism underlying the cross-talk between CBD-A and -B, we report here the NMR investigation of a construct of R, RIalpha-(119-379), which unlike previous fragments characterized by NMR, spans in full both CBDs. Our NMR studies were also extended to two mutants, R209K and the corresponding R333K, which severely reduce the affinity of cAMP for CBD-A and -B, respectively. The comparative NMR analysis of wild-type RIalpha-(119-379) and of the two domain silencing mutations has led to the definition at an unprecedented level of detail of both intra- and interdomain allosteric networks, revealing several striking differences between the two CBDs. First, the two domains, although homologous in sequence and structure, exhibit remarkably different responses to the R/K mutations especially at the beta2-3 allosteric "hot spot." Second, although the two CBDs are reciprocally coupled at the level of local unfolding of the hinge, the A-to-B and B-to-A pathways are dramatically asymmetrical at the level of global unfolding. Such an asymmetric interdomain cross-talk ensures efficiency and robustness in both the activation and de-activation of PKA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.