Abstract
Farnesyl (Far) and palmitoyl (Pal) anchors play important roles in the traffic of many lipidated proteins. Herein, we show the distinctive interactions and influences of the two lipid modifications on lipid rafts (LRs) and non-raft-like membranes using molecular dynamics simulations. Palmitoyl anchors behave in a more ordered fashion, pack tighter with the lipids of LRs and diffuse at a slower rate than farnesyl anchors in LRs. When interacting with non-raft-like membranes these two types of anchors become less ordered, pack more loosely with lipids, and diffuse at a higher rate. By calculating both the number of contacts per chain and the number of contact atoms per carbon of the two anchors with the lipid components, we found that the palmitoyl chains preferred to associate with the saturated chains of lipids and cholesterol molecules in LRs, while farnesyl chains favored association with saturated chains and unsaturated chains. For non-raft-like membranes, these two lipid anchors had roughly the same preference for the three types of contact lipid chains. Additionally, palmitoyl anchors caused cholesterol to orient more perpendicular to the membrane surface, surrounding lipids to become more ordered, and lipid lateral fluidity to reduce significantly, compared to farnesyl anchors in LRs. By contrast, the POPE and DSPC became much less ordered, cholesterol became more tilted, and lipids became more fluid, when the two types lipid anchors were inserted in non-raft-like membranes. These findings are useful for understanding the traffic mechanisms of lipidated proteins with farnesyl and palmitoyl modifications in cell membranes.
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Acknowledgements
The work was supported in part by the Ministry of Science and Technology of China (2012CB518005 and 2015CB910304), the National Natural Science Foundation of China (21422208), E-Institutes of Shanghai Municipal Education Commission (E09013), and Institutes for Drug Discovery and Development, Chinese Academy of Sciences.
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Zhang, T., Luo, Q., Yang, L. et al. Characterizing the interactions of two lipid modifications with lipid rafts: farnesyl anchors vs. palmitoyl anchors. Eur Biophys J 47, 19–30 (2018). https://doi.org/10.1007/s00249-017-1217-7
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DOI: https://doi.org/10.1007/s00249-017-1217-7