Insights into the behavior of unsaturated diacylglycerols in mixed lipid bilayers in relation to protein kinase C activation-A molecular dynamics simulation study.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101731713 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-2642 (Electronic) Linking ISSN: 00052736 NLM ISO Abbreviation: Biochim Biophys Acta Biomembr Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier
    • Subject Terms:
      Diglycerides*/metabolism ; Lipid Bilayers*/metabolism; Cholesterol ; Molecular Dynamics Simulation ; Phosphatidylcholines ; Protein Kinase C/metabolism
    • Abstract:
      The lipid second messenger diacylglycerol (DAG) is known for its involvement in many types of cellular signaling, especially as an endogenous agonist for protein kinase C (PKC). Evidence has emerged that the degree of saturation of the DAG molecules can affect PKC activation. DAG molecules with different acyl chain saturation have not only been observed to induce varying extents of PKC activation, but also to express selectivity towards different PKC isozymes. Both qualities are important for precise therapeutic activation of PKC; understanding DAG behavior at the molecular level in different environments has much potential in the development of drugs to target PKC. We used molecular dynamics simulations to study the behavior of two different unsaturated DAG species in lipid environments with varying degrees of unsaturation. We focus on phosphatidylethanolamine (PE) instead of phosphatidylcholine (PC) to more accurately model the relevant biomembranes. The effect of cholesterol (CHOL) on these systems was also explored. We found that both high level of unsaturation in the acyl chains of the DAG species and presence of CHOL in the surrounding membrane increase DAG molecule availability at the lipid-water interface. This can partially explain the previously observed differences in PKC activation strength and specificity, the complete mechanism is, however, likely to be more complex. Our simulations coupled with the current understanding of lipids highlight the need for more simulations of biologically accurate lipid environments in order to determine the correct correlations between molecular mechanisms and biological behavior when studying PKC activation.
      (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Acyl tail unsaturation; Diacylglycerol; Lipid bilayer; Lipid signaling; Molecular dynamics simulation; Protein kinase C
    • Accession Number:
      0 (Diglycerides)
      0 (Lipid Bilayers)
      0 (Phosphatidylcholines)
      97C5T2UQ7J (Cholesterol)
      EC 2.7.11.13 (Protein Kinase C)
    • Publication Date:
      Date Created: 20220514 Date Completed: 20220617 Latest Revision: 20220708
    • Publication Date:
      20221213
    • Accession Number:
      10.1016/j.bbamem.2022.183961
    • Accession Number:
      35568204