Bacterial Model Membranes Reshape Fibrillation of a Functional Amyloid Protein
Bacterial Model Membranes Reshape Fibrillation of a Functional Amyloid Protein
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DOI：
10.1021/acs.biochem.8b00002
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发表时间：
2018-09-04
期刊：
影响因子：
2.9
通讯作者：
Chai, Liraz
中科院分区：
文献类型：
--
作者：
Malishev, Ravit;Abbasi, Razan;Chai, Liraz
生物膜是形成表面相关群落的细胞聚集体。生物膜中的细胞与细胞外基质相互连接，细胞外基质是一个主要由多糖、蛋白质，有时还有核酸组成的网络。一些细胞外基质蛋白形成纤维，称为功能性淀粉样蛋白或类淀粉样蛋白，以将其结构功能与疾病相关的淀粉样蛋白纤维区分开来。最近的功能性淀粉样蛋白组装研究忽略了它们与膜的相互作用，尽管它们是在细胞环境中天然形成的。在这里，我们使用土壤细菌枯草芽孢杆菌生物膜中的主要基质蛋白 TasA 作为模型功能性淀粉样蛋白，并探究细菌功能性淀粉样蛋白是否与膜相互作用。使用生化、光谱和显微工具，我们表明 TasA 与细菌模型膜有独特的相互作用，并且这种相互作用相互影响蛋白质和膜的形态和结构。在蛋白质水平上，在没有膜和存在真核模型膜的情况下形成具有相似结构和形态的纤维。然而，在细菌模型膜存在的情况下，TasA 会形成具有不同 β 片层特征的无序聚集体。在膜水平上，荧光显微镜和各向异性测量表明，在与 TasA 相互作用时，细菌膜比真核细胞膜变形更大。我们的研究结果表明，TasA 比真核模型膜更能穿透细菌膜，这会导致膜破裂并重塑 TasA 纤维形成途径。考虑到 TasA 在提供生物膜完整性方面的重要作用，我们的研究可能会指导针对蛋白质-膜界面的抗生物膜药物的设计。
Biofilms are aggregates of cells that form surface-associated communities. The cells in biofilms are interconnected with an extracellular matrix, a network that is made mostly of polysaccharides, proteins, and sometimes nucleic acids. Some extracellular matrix proteins form fibers, termed functional amyloid or amyloid-like, to differentiate their constructive function from disease-related amyloid fibers. Recent functional amyloid assembly studies have neglected their interaction with membranes, despite their native formation in a cellular environment. Here, we use TasA, a major matrix protein in biofilms of the soil bacterium Bacillus subtilis, as a model functional amyloid protein and ask whether the bacterial functional amyloid interacts with membranes. Using biochemical, spectroscopic, and microscopic tools, we show that TasA interacts distinctively with bacterial model membranes and that this interaction mutually influences the morphology and structure of the protein and the membranes. At the protein level, fibers of similar structure and morphology are formed in the absence of membranes and in the presence of eukaryotic model membranes. However, in the presence of bacterial model membranes, TasA forms disordered aggregates with a different beta sheet signature. At the membrane level, fluorescence microscopy and anisotropy measurements indicate that bacterial membranes deform more considerably than eukaryotic membranes upon interaction with TasA. Our findings suggest that TasA penetrates bacterial more than eukaryotic model membranes and that this leads to membrane disruption and to reshaping the TasA fiber formation pathway. Considering the important role of TasA in providing integrity to biofilms, our study may direct the design of antibiofilm drugs to the protein-membrane interface.