Molecular Neuropharmacology Group, Department of Neuroscience and Pharmacology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
FEBS Lett. 2010 May 3;584(9):1848-55. doi: 10.1016/j.febslet.2010.01.053. Epub 2010 Jan 31.
The internal membranes of eukaryotic cells are all twists and bends characterized by high curvature. During recent years it has become clear that specific proteins sustain these curvatures while others simply recognize membrane shape and use it as "molecular information" to organize cellular processes in space and time. Here we discuss this new important recognition process termed membrane curvature sensing (MCS). First, we review a new fluorescence-based experimental method that allows characterization of MCS using measurements on single vesicles and compare it to sensing assays that use bulk/ensemble liposome samples of different mean diameter. Next, we describe two different MCS protein motifs (amphipathic helices and BAR domains) and suggest that in both cases curvature sensitive membrane binding results from asymmetric insertion of hydrophobic amino acids in the lipid membrane. This mechanism can be extended to include the insertion of alkyl chain in the lipid membrane and consequently palmitoylated and myristoylated proteins are predicted to display similar curvature sensitive binding. Surprisingly, in all the aforementioned cases, MCS is predominantly mediated by a higher density of binding sites on curved membranes instead of higher affinity as assumed so far. Finally, we integrate these new insights into the debate about which motifs are involved in sensing versus induction of membrane curvature and what role MCS proteins may play in biology.
真核细胞的内细胞膜都是高度弯曲的扭曲和弯曲，具有高曲率。近年来，人们已经清楚地认识到，特定的蛋白质维持这些曲率，而其他蛋白质只是识别膜的形状，并将其用作“分子信息”，在空间和时间上组织细胞过程。在这里，我们讨论了这个新的重要识别过程，称为膜曲率感应（MCS）。首先，我们回顾了一种新的基于荧光的实验方法，该方法允许使用对单个囊泡的测量来表征 MCS，并将其与使用不同平均直径的批量/整体脂质体样品的感应测定进行比较。接下来，我们描述了两种不同的 MCS 蛋白基序（两亲性螺旋和 BAR 结构域），并提出在这两种情况下，曲率敏感的膜结合都是由于疏水性氨基酸在脂质膜中的不对称插入引起的。该机制可以扩展到包括在脂质膜中插入烷基链，因此预测棕榈酰化和豆蔻酰化蛋白具有类似的曲率敏感结合。令人惊讶的是，在所有上述情况下，MCS 主要是通过弯曲膜上更高密度的结合位点介导的，而不是迄今为止假设的更高亲和力。最后，我们将这些新的见解整合到关于哪些基序参与膜曲率的感应和诱导的争论中，并探讨 MCS 蛋白在生物学中可能扮演的角色。
