ArticleJournal of the American Chemical Society2014
Interactions of protein kinase C-α C1A and C1B domains with membranes: a combined computational and experimental study.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- LDI, A Lipid Droplet Inhibitor, Disrupts Lipid Accumulation and Modulates Hepatic Lipid Profiles in Fatty Liver.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- PDK1:PKCα heterodimer association-dissociation dynamics in single-molecule diffusion tracks on a target membrane.Biophysical journal · 2023Article
- Expanding the Paradigm of Structure-Based Drug Design: Molecular Dynamics Simulations Support the Development of New Pyridine-Based Protein Kinase C-Targeted Agonists.Journal of medicinal chemistry · 2023Article
- Insertion Depth Modulates Protein Kinase C-δ-C1b Domain Interactions with Membrane Cholesterol as Revealed by MD Simulations.International journal of molecular sciences · 2023Article
- Structural anatomy of Protein Kinase C C1 domain interactions with diacylglycerol and other agonists.Nature communications · 2022Article
- Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Structural insights into C1-ligand interactions: Filling the gaps by in silico methods.Advances in biological regulation · 2021Review
- Anionic Lipids Impact RAS-Binding Site Accessibility and Membrane Binding Affinity of CRAF RBD-CRD.Biophysical journal · 2020Article
- Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance.Chemical reviews · 2019Article
- Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation.Chemical reviews · 2019Review
- Molecular recognition of RAS/RAF complex at the membrane: Role of RAF cysteine-rich domain.Scientific reports · 2018Article
- REDOR NMR Reveals Multiple Conformers for a Protein Kinase C Ligand in a Membrane Environment.ACS central science · 2018Article
- Synthesis and Evaluation of Dimeric Derivatives of Diacylglycerol-Lactones as Protein Kinase C Ligands.Bioconjugate chemistry · 2017Article
- Toggling of Diacylglycerol Affinity Correlates with Conformational Plasticity in C1 Domains.Biochemistry · 2017Article
- Molecular dynamics simulations reveal ligand-controlled positioning of a peripheral protein complex in membranes.Nature communications · 2017Article
- Highly Coarse-Grained Representations of Transmembrane Proteins.Journal of chemical theory and computation · 2017Article
- Computational and theoretical approaches for studies of a lipid recognition protein on biological membranes.Biophysics and physicobiology · 2017Review
- 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
- Protein Kinase Cα (PKCα) Is Resistant to Long Term Desensitization/Down-regulation by Prolonged Diacylglycerol Stimulation.The Journal of biological chemistry · 2016Article
- Dynamics and Membrane Interactions of Protein Kinase C.Biochemistry · 2015Review
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Protein kinase C-α (PKCα) has been studied widely as a paradigm for conventional PKCs, with two C1 domains (C1A and C1B) being important for the regulation and function of the kinase. However, it is challenging to explore these domains in membrane-bound environments with either simulations or experiments alone. In this work, we have combined modeling, simulations, and experiments to understand the molecular basis of the PKCα C1A and C1B domain interactions with membranes. Our atomistic simulations of the PKCα C1 domains reveal the dynamic interactions of the proteins with anionic lipids, as well as the conserved hydrogen bonds and the distinct nonpolar contacts formed with lipid activators. Corroborating evidence is obtained from additional simulations and experiments in terms of lipid binding and protein diffusion. Overall, our study, for the first time, explains with atomistic detail how the PKCα C1A and C1B domains interact differently with various lipids. On the molecular level, the information provided by our study helps to shed light on PKCα regulation and activation mechanism. The combined computational/experimental approach demonstrated in this work is anticipated to enable further studies to explore the roles of C1 domains in many signaling proteins and to better understand their molecular mechanisms in normal cellular function and disease development.
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