Chaperones directly and efficiently disperse stress-triggered biomolecular condensates.
Chaperones directly and efficiently disperse stress-triggered biomolecular condensates.
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DOI：
10.1016/j.molcel.2022.01.005
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发表时间：
2022-02-17
期刊：
影响因子：
16
通讯作者：
Drummond DA
中科院分区：
文献类型：
--
作者：
Yoo H;Bard JAM;Pilipenko EV;Drummond DA
热休克等应激会触发蛋白质聚集体的形成，并诱导由分子伴侣组成的解聚系统。最近的研究表明，一些明显的热诱导聚集的情况长期以来被认为是有毒错误折叠的结果，但实际上反映了进化的、适应性的生物分子凝聚，其中伴侣活性有助于凝聚调节。在这里，我们表明，酵母解聚系统直接分散热诱导的内源性多聚腺苷酸结合蛋白（Pab1）生物分子凝聚物，其速度比最常用的错误折叠模型底物萤火虫荧光素酶的聚集体快几个数量级。除了效率之外，热诱导冷凝物分散与热诱导骨料分散的不同之处在于其分子要求和机械行为。我们的工作为长期研究的热休克蛋白建立了真正的内源性热诱导底物，分离了凝结物伴侣调节的具体例子，并强调需要扩展热休克反应的蛋白毒性解释以涵盖适应性、伴侣介导的调节。
Stresses such as heat shock trigger formation of protein aggregates and induction of a disaggregation system composed of molecular chaperones. Recent work reveals that several cases of apparent heat-induced aggregation, long thought to be the result of toxic misfolding, instead reflect evolved, adaptive biomolecular condensation, with chaperone activity contributing to condensate regulation. Here, we show that the yeast disaggregation system directly disperses heat-induced biomolecular condensates of endogenous poly(A)-binding protein (Pab1) orders of magnitude more rapidly than aggregates of the most commonly used misfolded model substrate, firefly luciferase. Beyond its efficiency, heat-induced condensate dispersal differs from heat-induced aggregate dispersal in its molecular requirements and mechanistic behavior. Our work establishes a bona fide endogenous heat-induced substrate for long-studied heat shock proteins, isolates a specific example of chaperone regulation of condensates, and underscores needed expansion of the proteotoxic interpretation of the heat shock response to encompass adaptive, chaperone-mediated regulation.
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