Akbey Ümit, Andreasen Maria
Department of Structural Biology, School of Medicine, University of Pittsburgh Pittsburgh PA 15261 USA
Department of Biomedicine, Aarhus University Wilhelm Meyers Allé 3 8000 Aarhus Denmark
Chem Sci. 2022 May 6;13(22):6457-6477. doi: 10.1039/d2sc00645f. eCollection 2022 Jun 7.
Protein aggregation and amyloid formation have historically been linked with various diseases such as Alzheimer's and Parkinson's disease, but recently functional amyloids have gained a great deal of interest in not causing a disease and having a distinct function . Functional bacterial amyloids form the structural scaffold in bacterial biofilms and provide a survival strategy for the bacteria along with antibiotic resistance. The formation of functional amyloids happens extracellularly which differs from most disease related amyloids. Studies of functional amyloids have revealed several distinctions compared to disease related amyloids including primary structures designed to optimize amyloid formation while still retaining a controlled assembly of the individual subunits into classical cross-β-sheet structures, along with a unique cross-α-sheet amyloid fold. Studies have revealed that functional amyloids interact with components found in the extracellular matrix space such as lipids from membranes and polymers from the biofilm. Intriguingly, a level of complexity is added as functional amyloids also interact with several disease related amyloids and a causative link has even been established between functional amyloids and neurodegenerative diseases. It is hence becoming increasingly clear that functional amyloids are not inert protein structures found in bacterial biofilms but interact with many different components including human proteins related to pathology. Gaining a clear understanding of the factors governing the interactions will lead to improved strategies to combat biofilm associated infections and the correlated antibiotic resistance. In the current review we summarize the current state of the art knowledge on this exciting and fast growing research field of biofilm forming bacterial functional amyloids, their structural features and interaction partners.
蛋白质聚集和淀粉样蛋白形成在历史上一直与各种疾病相关联，如阿尔茨海默病和帕金森病，但最近功能性淀粉样蛋白引起了人们极大的兴趣，因为它们不会引发疾病且具有独特功能。功能性细菌淀粉样蛋白构成细菌生物膜的结构支架，并为细菌提供生存策略以及抗生素抗性。功能性淀粉样蛋白的形成发生在细胞外，这与大多数与疾病相关的淀粉样蛋白不同。对功能性淀粉样蛋白的研究揭示了与疾病相关淀粉样蛋白相比的几个区别，包括旨在优化淀粉样蛋白形成同时仍保持各个亚基可控组装成经典交叉β-折叠结构的一级结构，以及独特的交叉α-折叠淀粉样蛋白结构。研究表明，功能性淀粉样蛋白与细胞外基质空间中发现的成分相互作用，如膜中的脂质和生物膜中的聚合物。有趣的是，功能性淀粉样蛋白还与几种与疾病相关的淀粉样蛋白相互作用，增加了一层复杂性，甚至在功能性淀粉样蛋白与神经退行性疾病之间建立了因果联系。因此，越来越清楚的是，功能性淀粉样蛋白不是在细菌生物膜中发现的惰性蛋白质结构，而是与许多不同成分相互作用，包括与病理学相关的人类蛋白质。清楚了解控制这些相互作用的因素将有助于改进对抗生物膜相关感染和相关抗生素抗性的策略。在本综述中，我们总结了关于形成生物膜的细菌功能性淀粉样蛋白这一令人兴奋且快速发展的研究领域的现有最新知识、它们的结构特征和相互作用伙伴。
