González-Rubio Paula, Gautier Romain, Etchebest Catherine, Fuchs Patrick F J
INSERM UMR-S665, DSIMB, F-75015, Paris, France.
Biochim Biophys Acta. 2011 Sep;1808(9):2119-27. doi: 10.1016/j.bbamem.2011.05.006. Epub 2011 May 12.
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.
两亲性脂质堆积传感器（ALPS）基序在高尔基体囊泡形成过程中将蛋白ArfGAP1靶向到弯曲膜上。由于出芽囊泡的正曲率，ALPS特异性识别脂质堆积缺陷。在这项工作中，我们通过显式分子动力学（MD）评估了ALPS与两种具有不同脂质堆积程度的磷脂膜之间的微观相互作用。模拟在由摩尔比为85:15的二油酰磷脂酰胆碱（DOPC）/二油酰甘油（DOG）混合物组成的疏松堆积膜内进行。其他一些模拟在脂质堆积更紧密的纯DOPC中进行。我们表明，DOG的存在会在磷酸水平上导致堆积缺陷，从而改变双层膜的一些性质。这导致脂质头部基团的水合作用增强。当嵌入具有此类缺陷的膜中时，ALPS比在堆积更紧密的膜中表现出更高程度的构象灵活性。我们提出，ALPS对脂质堆积的感知可能具有熵起源，并且其灵活性是一个关键特征。
