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°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.

蛋白质通常通过在接近沸腾的温度下加热而变性和聚集。这一原则的例外包括在极端微生物中发现的高度无序和耐热的蛋白质，这些蛋白质帮助这些生物体耐受干燥、冷冻和高盐度等极端条件。相比之下，热溶蛋白在包括人类在内的非极端生物体中的功能在很大程度上仍未被探索。在这里，我们报道了耐热模糊（英雄）蛋白质，它们在 95°C 煮沸后仍然可溶，在果蝇和人类中广泛存在。英雄蛋白具有亲水性和高电荷，具有稳定各种“客户”蛋白的作用，即使在热休克、干燥和暴露于有机溶剂等应激条件下也能保护它们免于变性。英雄蛋白还可以阻断细胞和模拟神经退行性疾病的果蝇菌株中几种不同类型的病理蛋白聚集。此外，英雄蛋白可以延长果蝇的寿命。我们的研究表明，生物体自然地使用英雄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。