ArticleNature communications2019
Activation of PKA via asymmetric allosteric coupling of structurally conserved cyclic nucleotide binding domains.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Harnessing virtual screening and MD simulations: a multistage approach to identifying potent and nontoxic agonists for protein kinase A.Molecular diversity · 2026Article
- N3A motifs in RIβ mediate allosteric crosstalk between cAMP and ATP in PKA activation.Protein science : a publication of the Protein Society · 2025Article
- Neuronal glycogen breakdown mitigates tauopathy via pentose-phosphate-pathway-mediated oxidative stress reduction.Nature metabolism · 2025Article
- Decoding allosteric landscapes: computational methodologies for enzyme modulation and drug discovery.RSC chemical biology · 2025Review
- One-pot dual protein labeling for simultaneous mechanical and fluorescent readouts in optical tweezers.Protein science : a publication of the Protein Society · 2025Article
- 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
- The cofactor-dependent folding mechanism of Drosophila cryptochrome revealed by single-molecule pulling experiments.Nature communications · 2023Article
- Joint neutron/molecular dynamics vibrational spectroscopy reveals softening of HIV-1 protease upon binding of a tight inhibitor.Physical chemistry chemical physics : PCCP · 2022Article
- Using Optical Tweezers to Monitor Allosteric Signals Through Changes in Folding Energy Landscapes.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Multi-start Evolutionary Nonlinear OpTimizeR (MENOTR): A hybrid parameter optimization toolbox.Biophysical chemistry · 2021Article
- Article
- Out-of-Equilibrium Biophysical Chemistry: The Case for Multidimensional, Integrated Single-Molecule Approaches.The journal of physical chemistry. B · 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
- Effects of Ligand Binding on the Energy Landscape of Acyl-CoA-Binding Protein.Biophysical journal · 2020Article
- Allosteric pluripotency as revealed by protein kinase A.Science advances · 2020Article
- Distinct chromophore-protein environments enable asymmetric activation of a bacteriophytochrome-activated diguanylate cyclase.The Journal of biological chemistry · 2020Article
- From structure to the dynamic regulation of a molecular switch: A journey over 3 decades.The Journal of biological chemistryReview
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Authors and funding
7 authors.
Funding
Abstract
Cyclic nucleotide-binding (CNB) domains allosterically regulate the activity of proteins with diverse functions, but the mechanisms that enable the cyclic nucleotide-binding signal to regulate distant domains are not well understood. Here we use optical tweezers and molecular dynamics to dissect changes in folding energy landscape associated with cAMP-binding signals transduced between the two CNB domains of protein kinase A (PKA). We find that the response of the energy landscape upon cAMP binding is domain specific, resulting in unique but mutually coordinated tasks: one CNB domain initiates cAMP binding and cooperativity, whereas the other triggers inter-domain interactions that promote the active conformation. Inter-domain interactions occur in a stepwise manner, beginning in intermediate-liganded states between apo and cAMP-bound domains. Moreover, we identify a cAMP-responsive switch, the N3A motif, whose conformation and stability depend on cAMP occupancy. This switch serves as a signaling hub, amplifying cAMP-binding signals during PKA activation.
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Registered trials
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.