ArticleJournal of molecular biology2011
Probing the determinants of diacylglycerol binding affinity in the C1B domain of protein kinase Cα.
Article in Journal of molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Structural anatomy of Protein Kinase C C1 domain interactions with diacylglycerol and other agonists.Nature communications · 2022Article
- Probing the Diacylglycerol Binding Site of Presynaptic Munc13-1.Biochemistry · 2021Article
- Reactivity of Thiol-Rich Zn Sites in Diacylglycerol-Sensing PKC C1 Domain Probed by NMR Spectroscopy.Frontiers in molecular biosciences · 2021Article
- Structural insights into C1-ligand interactions: Filling the gaps by in silico methods.Advances in biological regulation · 2021Review
- Structural determinants of phorbol ester binding activity of the C1a and C1b domains of protein kinase C theta.Biochimica et biophysica acta. Biomembranes · 2018Article
- REDOR NMR Reveals Multiple Conformers for a Protein Kinase C Ligand in a Membrane Environment.ACS central science · 2018Article
- Exploring the influence of indololactone structure on selectivity for binding to the C1 domains of PKCα, PKCε, and RasGRP.Bioorganic & medicinal chemistry · 2017Article
- Toggling of Diacylglycerol Affinity Correlates with Conformational Plasticity in C1 Domains.Biochemistry · 2017Article
- Structural Basis for the Failure of the C1 Domain of Ras Guanine Nucleotide Releasing Protein 2 (RasGRP2) to Bind Phorbol Ester with High Affinity.The Journal of biological chemistry · 2016Article
- Dynamics and Membrane Interactions of Protein Kinase C.Biochemistry · 2015Review
- Toward a biorelevant structure of protein kinase C bound modulators: design, synthesis, and evaluation of labeled bryostatin analogues for analysis with rotational echo double resonance NMR spectroscopy.Journal of the American Chemical Society · 2015Article
- Interfacial partitioning of a loop hinge residue contributes to diacylglycerol affinity of conserved region 1 domains.The Journal of biological chemistry · 2014Article
- Interactions of protein kinase C-α C1A and C1B domains with membranes: a combined computational and experimental study.Journal of the American Chemical Society · 2014Article
- Intramolecular conformational changes optimize protein kinase C signaling.Chemistry & biology · 2014Article
- Identification of the activator-binding residues in the second cysteine-rich regulatory domain of protein kinase Cθ (PKCθ).The Biochemical journal · 2013Article
- The C-terminal V5 domain of Protein Kinase Cα is intrinsically disordered, with propensity to associate with a membrane mimetic.PloS one · 2013Article
- Reactive cysteine in the structural Zn(2+) site of the C1B domain from PKCα.Biochemistry · 2012Article
- Molecular basis for failure of "atypical" C1 domain of Vav1 to bind diacylglycerol/phorbol ester.The Journal of biological chemistry · 2012Article
- AMP-activated protein kinase β-subunit requires internal motion for optimal carbohydrate binding.Biophysical journal · 2012Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
C1 domains are independently folded modules that are responsible for targeting their parent proteins to lipid membranes containing diacylglycerol (DAG), a ubiquitous second messenger. The DAG binding affinities of C1 domains determine the threshold concentration of DAG required for the propagation of signaling response and the selectivity of this response among DAG receptors in the cell. The structural information currently available for C1 domains offers little insight into the molecular basis of their differential DAG binding affinities. In this work, we characterized the C1B domain of protein kinase Cα (C1Bα) and its diagnostic mutant, Y123W, using solution NMR methods and molecular dynamics simulations. The mutation did not perturb the C1Bα structure or the sub-nanosecond dynamics of the protein backbone, but resulted in a >100-fold increase in DAG binding affinity and a substantial change in microsecond timescale conformational dynamics, as quantified by NMR rotating-frame relaxation-dispersion methods. The differences in the conformational exchange behavior between wild type and Y123W C1Bα were localized to the hinge regions of ligand-binding loops. Molecular dynamics simulations provided insight into the identity of the exchanging conformers and revealed the significance of a particular residue (Gln128) in modulating the geometry of the ligand-binding site. Taken together with the results of binding studies, our findings suggest that the conformational dynamics and preferential partitioning of the tryptophan side chain into the water-lipid interface are important factors that modulate the DAG binding properties of the C1 domains.
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