Structure, assembly, and biological activity of amyloid peptides and proteins.

淀粉样肽和蛋白质的结构、组装和生物活性。

• 批准号: 342069-2013
• 负责人: Sharpe, Simon
• 金额: $ 3.13万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=527570
• 关键词: Structure; assembly; biological; activity; amyloid

Amyloid fibrils are highly ordered filamentous structures formed by a wide range of different proteins and peptides. These assemblies were originally described as potential mediators of cytotoxicity in amyloidosis, and are linked to infectivity in prion diseases. More recently, amyloids been shown to play important functional roles in diverse biological processes ranging from assembly of the skin pigment melanin, genetic diversification of fungi and yeast and adhesion of bacteria and yeast to surfaces during biofilm formation. Despite their biological importance, the ability of diverse proteins to self-assemble into closely related structures having highly divergent function remains poorly understood. Similarly, it is not known how some of these assemblies can be potently cytotoxic while others avoid toxicity to perform biological tasks. This chemical and functional diversity, built on an ordered scaffold, is also a desirable feature in the development of novel biomaterials. Understanding the roles of amyloid proteins in biology, and exploiting their materials potential, both require detailed knowledge of the molecular basis for fibril formation, and the ability to link sequence with the structure and function of the fibrillar state.

淀粉样原纤维是由多种不同的蛋白质和肽形成的高度有序的丝状结构。 这些组件最初被描述为淀粉样变性中细胞毒性的潜在介质，并与朊病毒疾病的感染性有关。 最近，淀粉样蛋白被证明在各种生物过程中发挥重要的功能作用，从皮肤色素黑色素的组装，真菌和酵母的遗传多样性以及细菌和酵母在生物膜形成期间粘附到表面。 尽管其生物学的重要性，不同的蛋白质的能力，自组装成密切相关的结构具有高度不同的功能仍然知之甚少。 类似地，尚不清楚这些组件中的一些组件如何具有强效细胞毒性，而另一些组件如何避免毒性以执行生物学任务。 这种建立在有序支架上的化学和功能多样性也是开发新型生物材料的理想特征。 了解淀粉样蛋白在生物学中的作用，并利用其材料潜力，都需要详细了解原纤维形成的分子基础，以及将序列与原纤维状态的结构和功能联系起来的能力。