Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1343-8. doi: 10.1073/pnas.1009362108. Epub 2011 Jan 4.
Cell membranes are comprised of multicomponent lipid and protein mixtures that exhibit a complex partitioning behavior. Regions of structural and compositional heterogeneity play a major role in the sorting and self-assembly of proteins, and their clustering into higher-order oligomers. Here, we use computer simulations and optical microscopy to study the sorting of transmembrane helices into the liquid-disordered domains of phase-separated model membranes, irrespective of peptide-lipid hydrophobic mismatch. Free energy calculations show that the enthalpic contribution due to the packing of the lipids drives the lateral sorting of the helices. Hydrophobic mismatch regulates the clustering into either small dynamic or large static aggregates. These results reveal important molecular driving forces for the lateral organization and self-assembly of transmembrane helices in heterogeneous model membranes, with implications for the formation of functional protein complexes in real cells.
细胞膜由多组分脂质和蛋白质混合物组成，表现出复杂的分配行为。结构和组成异质性区域在蛋白质的分类和自组装及其聚类成更高阶的寡聚物中起着主要作用。在这里，我们使用计算机模拟和光学显微镜研究跨膜螺旋在相分离模型膜的无序域中的分类，而不考虑肽-脂质疏水性失配。自由能计算表明，由于脂质的包装引起的焓贡献驱动螺旋的横向分类。疏水性失配调节成小的动态或大的静态聚集体的聚类。这些结果揭示了异质模型膜中跨膜螺旋的横向组织和自组装的重要分子驱动力，对真核细胞中功能性蛋白质复合物的形成具有重要意义。
