A widespread family of heat-resistant obscure (Hero) proteins protect against protein instability and aggregation
A widespread family of heat-resistant obscure (Hero) proteins protect against protein instability and aggregation
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DOI：
10.1371/journal.pbio.3000632
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发表时间：
2020-03-01
期刊：
影响因子：
9.8
通讯作者：
Tomari, Yukihide
中科院分区：
文献类型：
--
作者：
Tsuboyama, Kotaro;Osaki, Tatsuya;Tomari, Yukihide
蛋白质通常通过在接近沸点的温度下加热而变性和聚集。极端微生物中发现的高度无序和耐热的蛋白质，有助于这些生物耐受干燥，冷冻和高盐度等极端条件。相比之下，包括人类在内的非极端生物中的热溶性蛋白质的功能在很大程度上仍未被探索。在这里，我们报告说，耐热模糊（英雄）蛋白质，在95摄氏度煮沸后仍然可溶，广泛存在于果蝇和人类。Hero蛋白是亲水性和高电荷的，并且起到稳定各种“客户”蛋白的作用，即使在诸如热休克、干燥和暴露于有机溶剂的应激条件下也保护它们免于变性。Hero蛋白还可以阻断细胞和模拟神经退行性疾病的果蝇品系中几种不同类型的病理性蛋白质聚集。此外，Hero蛋白可以延长果蝇的寿命。我们的研究表明，生物体自然地使用Hero蛋白作为分子盾牌来稳定蛋白质功能，突出了它们的生物技术和治疗潜力。
Proteins are typically denatured and aggregated by heating at near-boiling temperature. Exceptions to this principle include highly disordered and heat-resistant proteins found in extremophiles, which help these organisms tolerate extreme conditions such as drying, freezing, and high salinity. In contrast, the functions of heat-soluble proteins in non-extremophilic organisms including humans remain largely unexplored. Here, we report that heat-resistant obscure (Hero) proteins, which remain soluble after boiling at 95 degrees C, are widespread in Drosophila and humans. Hero proteins are hydrophilic and highly charged, and function to stabilize various "client" proteins, protecting them from denaturation even under stress conditions such as heat shock, desiccation, and exposure to organic solvents. Hero proteins can also block several different types of pathological protein aggregations in cells and in Drosophila strains that model neurodegenerative diseases. Moreover, Hero proteins can extend life span of Drosophila. Our study reveals that organisms naturally use Hero proteins as molecular shields to stabilize protein functions, highlighting their biotechnological and therapeutic potential.