Biophysics Graduate Group, University of California, Davis, CA 95616, USA.
Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):6975-80. doi: 10.1073/pnas.1014579108. Epub 2011 Apr 7.
Biological membranes are complex, self-organized structures that define boundaries and compartmentalize space in living matter. Composed of a wide variety of lipid and protein molecules, these responsive surfaces mediate transmembrane signaling and material transport within the cell and with its environment. It is well known that lipid membrane properties change as a function of composition and phase state, and that protein-lipid interactions can induce changes in the membrane's properties and biochemical response. Here, molecular level changes in lipid organization induced by multivalent toxin binding were investigated using grazing incidence X-ray diffraction. Structural changes to lipid monolayers at the air-water interface and bilayers at the solid-water interface were studied before and after specific binding of cholera toxin to membrane embedded receptors. At biologically relevant surface pressures, protein binding perturbed lipid packing within monolayers and bilayers resulting in topological defects and the emergence of a new orientationally textured lipid phase. In bilayers this altered lipid order was transmitted from the receptor laden exterior membrane leaflet to the inner leaflet, representing a potential mechanism for lipid mediated outside-in signaling by multivalent protein binding. It is further hypothesized that cell-surface micro-domains exhibiting this type of lipid order may serve as nucleation sites for vesicle formation in clathrin independent endocytosis of cholera toxin.
生物膜是复杂的自组织结构，定义了生命物质的边界和空间分隔。这些响应表面由多种脂质和蛋白质分子组成，在细胞内及其环境中介导跨膜信号转导和物质运输。众所周知，脂质膜的性质随组成和相态状态而变化，并且蛋白质-脂质相互作用可以诱导膜性质和生化反应的变化。在这里，使用掠入射 X 射线衍射研究了多价毒素结合诱导的脂质组织的分子水平变化。在霍乱毒素特异性结合到膜嵌入受体之前和之后，研究了空气 - 水界面处的单层和固体 - 水界面处的双层的脂质单层的结构变化。在生物学相关的表面压力下，蛋白质结合使单层和双层中的脂质堆积受到干扰，导致拓扑缺陷和新的各向同性纹理脂质相的出现。在双层中，这种改变的脂质顺序从富含受体的外膜小叶传递到内膜小叶，代表了多价蛋白结合的脂质介导的外侧信号传导的潜在机制。进一步假设表现出这种脂质有序性的细胞表面微区可能作为霍乱毒素的网格蛋白独立内吞作用的囊泡形成的成核位点。
