German Cancer Research Center, Heidelberg, Germany.
Biophys Chem. 2010 Sep;151(1-2):34-8. doi: 10.1016/j.bpc.2010.04.009. Epub 2010 May 6.
Sorting of transmembrane proteins is a central task of the secretory pathway. Due to the lack of an organizing mastermind, the decision whether a protein participates in anterograde/retrograde transport or rather stays in its compartment has to be made by a self-organization process on the molecular scale. Minimizing the hydrophobic mismatch between a protein and the surrounding lipid bilayer has been shown to be an important determinant of protein localization. It has remained elusive, however, how mislocalized proteins sense that remote organelles may provide a better lipid environment, i.e. how proteins differentially control their journey along the secretory pathway. Here we show by coarse-grained membrane simulations that proteins partition into the lipid phase with the smallest hydrophobic mismatch on heterogeneous membranes while they cluster and even segregate as homo-oligomers according to their hydrophobic mismatch on a homogeneous bilayer. We propose that protein sorting is facilitated by stabilizing coat proteins at clusters of mislocalized proteins that experience a hydrophobic mismatch.
跨膜蛋白的分拣是分泌途径的一项核心任务。由于缺乏一个组织核心，蛋白质是否参与正向/逆向运输的决定必须在分子尺度上通过自组织过程来做出。减少蛋白质与周围脂质双层之间的疏水性失配已被证明是蛋白质定位的一个重要决定因素。然而，仍然不清楚错误定位的蛋白质如何感知远程细胞器可能提供更好的脂质环境，即蛋白质如何差异控制它们在分泌途径中的旅程。在这里，我们通过粗粒膜模拟表明，蛋白质在异质膜上会分配到疏水性失配最小的脂质相中，而在均匀双层膜上，它们会根据疏水性失配而聚集甚至分离成同源寡聚体。我们提出，通过在经历疏水性失配的错误定位蛋白质簇上稳定衣壳蛋白，有助于蛋白质分拣。
