ArticleeLife2020
Multi-state recognition pathway of the intrinsically disordered protein kinase inhibitor by protein kinase A.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Structural mechanism for noncanonical GPCR signaling in the Hedgehog pathway.Nature structural & molecular biology · 2026Article
- Structural insights and biophysical characterization of p90RSK2:ERK2 complex.The Biochemical journal · 2025Article
- Article
- Predicting the sequence-dependent backbone dynamics of intrinsically disordered proteins.eLife · 2024Article
- Predicting the Sequence-Dependent Backbone Dynamics of Intrinsically Disordered Proteins.bioRxiv : the preprint server for biology · 2024Article
- HYPK: A marginally disordered protein sensitive to charge decoration.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Protein Kinase Structure and Dynamics: Role of the αC-β4 Loop.bioRxiv : the preprint server for biology · 2023Article
- Clustering Heterogeneous Conformational Ensembles of Intrinsically Disordered Proteins with t-Distributed Stochastic Neighbor Embedding.Journal of chemical theory and computation · 2023Article
- Classification of Cushing's syndrome PKAc mutants based upon their ability to bind PKI.The Biochemical journal · 2023Article
- Edmond Fischer's kinase legacy: History of the protein kinase inhibitor and protein kinase A.IUBMB life · 2023Article
- A PKA inhibitor motif within SMOOTHENED controls Hedgehog signal transduction.Nature structural & molecular biology · 2022Article
- Article
- Raf Kinase Inhibitory Protein regulates the cAMP-dependent protein kinase signaling pathway through a positive feedback loop.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Is Disrupted Nucleotide-Substrate Cooperativity a Common Trait for Cushing's Syndrome Driving Mutations of Protein Kinase A?Journal of molecular biology · 2021Article
- Cell-type and subcellular compartment-specific APEX2 proximity labeling reveals activity-dependent nuclear proteome dynamics in the striatum.Nature communications · 2021Article
- Soluble Methane Monooxygenase Component Interactions Monitored byBiochemistry · 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
- Structural basis for allosteric control of the SERCA-Phospholamban membrane complex by CaeLife · 2021Article
- Protein Kinase Inhibitor Peptide as a Tool to Specifically Inhibit Protein Kinase A.Frontiers in physiology · 2020Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
In the nucleus, the spatiotemporal regulation of the catalytic subunit of cAMP-dependent protein kinase A (PKA-C) is orchestrated by an intrinsically disordered protein kinase inhibitor, PKI, which recruits the CRM1/RanGTP nuclear exporting complex. How the PKA-C/PKI complex assembles and recognizes CRM1/RanGTP is not well understood. Using NMR, SAXS, fluorescence, metadynamics, and Markov model analysis, we determined the multi-state recognition pathway for PKI. After a fast binding step in which PKA-C selects PKI's most competent conformations, PKI folds upon binding through a slow conformational rearrangement within the enzyme's binding pocket. The high-affinity and pseudo-substrate regions of PKI become more structured and the transient interactions with the kinase augment the helical content of the nuclear export sequence, which is then poised to recruit the CRM1/RanGTP complex for nuclear translocation. The multistate binding mechanism featured by PKA-C/PKI complex represents a paradigm on how disordered, ancillary proteins (or protein domains) are able to operate multiple functions such as inhibiting the kinase while recruiting other regulatory proteins for nuclear export.
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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.