ArticleThe Journal of biological chemistry2018
An N-terminally truncated form of cyclic GMP-dependent protein kinase Iα (PKG Iα) is monomeric and autoinhibited and provides a model for activation.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 12 citations in OpenAlex.
- Structural insights into selective small molecule activation of PKG1α.Communications biology · 2023Article
- Characterizing the Protein Isoforms ofInternational journal of molecular sciences · 2023Article
- Mechanism of allosteric inhibition in theThe Journal of biological chemistry · 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
- Oxidation of cysteine 117 stimulates constitutive activation of the type Iα cGMP-dependent protein kinase.The Journal of biological chemistry · 2018Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The type I cGMP-dependent protein kinases (PKG I) serve essential physiological functions, including smooth muscle relaxation, cardiac remodeling, and platelet aggregation. These enzymes form homodimers through their N-terminal dimerization domains, a feature implicated in regulating their cooperative activation. Previous investigations into the activation mechanisms of PKG I isoforms have been largely influenced by structures of the cAMP-dependent protein kinase (PKA). Here, we examined PKG Iα activation by cGMP and cAMP by engineering a monomeric form that lacks N-terminal residues 1-53 (Δ53). We found that the construct exists as a monomer as assessed by whole-protein MS, size-exclusion chromatography, and small-angle X-ray scattering (SAXS). Reconstruction of the SAXS 3D envelope indicates that Δ53 has a similar shape to the heterodimeric RIα-C complex of PKA. Moreover, we found that the Δ53 construct is autoinhibited in its cGMP-free state and can bind to and be activated by cGMP in a manner similar to full-length PKG Iα as assessed by surface plasmon resonance (SPR) spectroscopy. However, we found that the Δ53 variant does not exhibit cooperative activation, and its cyclic nucleotide selectivity is diminished. These findings support a model in which, despite structural similarities, PKG Iα activation is distinct from that of PKA, and its cooperativity is driven by in
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