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

被引:5
作者
Heinonen, Suvi [1 ]
Lautala, Saara [1 ]
Bunker, Artturi Koivuniemi Alex [1 ]
机构
[1] Univ Helsinki, Drug Res Program, Div Pharmaceut Biosci, FI-00014 Helsinki, Finland
来源
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES | 2022年 / 1864卷 / 09期
关键词
Diacylglycerol; Lipid signaling; Acyl tail unsaturation; Lipid bilayer; Protein kinase C; Molecular dynamics simulation; ALZHEIMERS-DISEASE; HEXAGONAL PHASE; CUBIC PHASE; ACYL-CHAIN; MEMBRANE; CHOLESTEROL; MODEL; PHOSPHATIDYLETHANOLAMINE; GROMACS; DOMAIN;
D O I
10.1016/j.bbamem.2022.183961
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:12
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