ArticleThe journal of physical chemistry. B2017
Investigation of the Effect of Bilayer Composition on PKCα-C2 Domain Docking Using Molecular Dynamics Simulations.
Article in The journal of physical chemistry. B, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Disease-causing mutations in Synaptotagmin can act via dominant-negative, gain-of-function or haploinsufficient mechanisms.bioRxiv : the preprint server for biology · 2026Article
- CaThe journal of physical chemistry. B · 2025Article
- Molecular Dynamics Simulations of the SNARE Complex Interacting with Synaptotagmin, Complexin, and Lipid Bilayers.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Dynamic formation of the protein-lipid prefusion complex.Biophysical journal · 2024Article
- Dynamic Formation of the Protein-Lipid Pre-fusion Complex.bioRxiv : the preprint server for biology · 2024Article
- Insertion Depth Modulates Protein Kinase C-δ-C1b Domain Interactions with Membrane Cholesterol as Revealed by MD Simulations.International journal of molecular sciences · 2023Article
- Analysis of the MCTP Amino Acid Sequence Reveals the Conservation of Putative Calcium- and Lipid-Binding Pockets Within the C2 Domains In Silico.Journal of molecular evolution · 2022Article
- Article
- Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Binding of CaStructure (London, England : 1993) · 2021Article
- SNARE complex alters the interactions of the CaBiophysical journal · 2021Article
- The Implications for Cells of the Lipid Switches Driven by Protein-Membrane Interactions and the Development of Membrane Lipid Therapy.International journal of molecular sciences · 2020Review
- The energetics of protein-lipid interactions as viewed by molecular simulations.Biochemical Society transactions · 2020Review
- Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation.Chemical reviews · 2019Review
- Lateral distribution of phosphatidylinositol 4,5-bisphosphate in membranes regulates formin- and ARP2/3-mediated actin nucleation.The Journal of biological chemistry · 2019Article
- Polyphosphoinositide-Binding Domains: Insights from Peripheral Membrane and Lipid-Transfer Proteins.Advances in experimental medicine and biology · 2019Review
- Phosphatidylinositol (4, 5)-bisphosphate targets double C2 domain protein B to the plasma membrane.Traffic (Copenhagen, Denmark) · 2017Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The protein kinase Cα (PKCα) enzyme is a member of a broad family of serine/threonine kinases, which are involved in varied cellular signaling pathways. The initial step of PKCα activation involves the C2 subunit docking with the cell membrane, which is followed by interactions of the C1 domains with diacylglycerol (DAG) in the membrane. Notably, the molecular mechanisms of these interactions remain poorly understood, especially what effects, if any, DAG may have on the initial C2 docking. To further understand this process, we have performed a series of conventional molecular dynamics simulations to systematically investigate the interaction between PKCα-C2 domains and lipid bilayers with different compositions to examine the effects of POPS, PIP2, and 1-palmitoyl-2-oleoyl-sn-glycerol (POG) on domain docking. Our results show that the PKCα-C2 domain does not interact with the bilayer surface in the absence of POPS and PIP2. In contrast, the inclusion of POPS and PIP2 to the bilayer resulted in strong domain docking in both perpendicular and parallel orientations, whereas the further inclusion of POG resulted in only parallel domain docking. In addition, lysine residues in the C2 domain formed hydrogen bonds with PIP2 molecule bilayers containing POG. These effects were further explored with umbrella sampling calculations to estimate the free energy of domain docking to the lipid bilayer in the presence of one or two PIP2 molecules. The results show that the binding of one or two PIP2 molecules is thermodynamically favorable, although stronger in bilayers lacking POG. However, in POG-containing bilayers, the binding mode of the C2 domain appears to be more flexible, which may have implications for activation of full-length PKCα. Together, our results shed new insights into the process of C2 bilayer binding and suggest new mechanisms for the roles of different phospholipids in the activation process of PKCα.
Indexed as
Identifiers
What OpenQuestion holds
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.