Laboratoire d'Enzymologie et Biochimie Structurales, Centre de Recherche de Gif, Centre National de la Recherche Scientifique 91198 Gif-sur-Yvette, France.
J Cell Biol. 2011 Jul 11;194(1):89-103. doi: 10.1083/jcb.201011118.
Membrane curvature sensors have diverse structures and chemistries, suggesting that they might have the intrinsic capacity to discriminate between different types of vesicles in cells. In this paper, we compare the in vitro and in vivo membrane-binding properties of two curvature sensors that form very different amphipathic helices: the amphipathic lipid-packing sensor (ALPS) motif of a Golgi vesicle tether and the synaptic vesicle protein α-synuclein, a causative agent of Parkinson's disease. We demonstrate the mechanism by which α-synuclein senses membrane curvature. Unlike ALPS motifs, α-synuclein has a poorly developed hydrophobic face, and this feature explains its dual sensitivity to negatively charged lipids and to membrane curvature. When expressed in yeast cells, these two curvature sensors were targeted to different classes of vesicles, those of the early secretory pathway for ALPS motifs and to negatively charged endocytic/post-Golgi vesicles in the case of α-synuclein. Through structures with complementary chemistries, α-synuclein and ALPS motifs target distinct vesicles in cells by direct interaction with different lipid environments.
膜曲率传感器具有不同的结构和化学性质，这表明它们可能具有内在的能力来区分细胞中不同类型的囊泡。在本文中，我们比较了两种形成非常不同的两亲性螺旋的曲率传感器的体外和体内膜结合特性：高尔基囊泡连接物的两亲性脂质堆积传感器（ALPS）基序和突触囊泡蛋白α-突触核蛋白，这是帕金森病的致病因子。我们证明了α-突触核蛋白感知膜曲率的机制。与 ALPS 基序不同，α-突触核蛋白具有不发达的疏水面，这一特征解释了其对带负电荷的脂质和膜曲率的双重敏感性。当在酵母细胞中表达时，这两种曲率传感器被靶向到不同类型的囊泡，ALPS 基序靶向早期分泌途径的囊泡，而α-突触核蛋白靶向带负电荷的内吞/高尔基体后囊泡。通过具有互补化学性质的结构，α-突触核蛋白和 ALPS 基序通过与不同的脂质环境直接相互作用，靶向细胞中的不同囊泡。
