The Amphipathic-Lipid-Packing-Sensor (ALPS) motif targets the protein ArfGAP1 to curved membranes during vesicle formation in the Golgi apparatus. ALPS specifically recognizes lipid packing defects due to the positive curvature of budding vesicles. In this work we assessed the microscopic interactions between ALPS and two phospholipid membranes at different degrees of lipid packing by explicit molecular dynamics (MD). Simulations were performed within loosely packed membranes composed of a mixture of dioleoylphosphatidylcholine (DOPC)/dioleoylglycerol (DOG) at a molar ratio 85:15. Some other simulations were performed in pure DOPC for which lipid packing is tighter. We show that the presence of DOG causes packing defects at the phosphate level and thereby modifies some properties of the bilayer. This leads to a higher hydration of the lipid headgroups. When embedded in a membrane with such defects, ALPS displays a higher degree of conformational flexibility than in a more packed membrane. We propose that lipid packing sensing by ALPS may have an entropic origin and that its flexibility is a key feature. © 2011 Elsevier B.V. All rights reserved.
González-Rubio, P., Gautier, R., Etchebest, C., & Fuchs, P. F. J. (2011). Amphipathic-Lipid-Packing-Sensor interactions with lipids assessed by atomistic molecular dynamics. Biochimica et Biophysica Acta - Biomembranes, 1808(9), 2119–2127. https://doi.org/10.1016/j.bbamem.2011.05.006