Reversible Kinetic Trapping of FUS Biomolecular Condensates.
Reversible Kinetic Trapping of FUS Biomolecular Condensates.
复制标题
DOI：
10.1002/advs.202104247
复制
发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Parekh SH
中科院分区：
文献类型：
--
作者：
Chatterjee S;Kan Y;Brzezinski M;Koynov K;Regy RM;Murthy AC;Burke KA;Michels JJ;Mittal J;Fawzi NL;Parekh SH
pH、盐或温度等外部刺激可以触发无序蛋白质自组装形成无膜细胞器。这些细胞器被称为生物分子凝聚物，传统上被分类为液体、凝胶或具有有限子类的固体。在这里，作者表明，热触发可以导致在肉瘤低复杂性（FUS LC）域中融合形成至少两个不同的液态凝聚相。在低温下直接形成 FUS LC 冷凝物会导致形成亚稳态、动力学捕获的冷凝物，这些冷凝物表现出抑制聚结的现象，可以通过热退火从其中逃逸到未捕获的冷凝物。通过实验和计算方法，作者发现，与未捕获的 FUS LC 冷凝物相比，动力学捕获的冷凝物中界面 FUS LC 的分子结构是不同的（更像 β 片层）。此外，与未捕获的冷凝物相比，动力学捕获的冷凝物内的分子运动要慢得多，从而证明了两种独特的液体 FUS 冷凝物。使用简单的热开关控制冷凝物的热力学状态、稳定性和结构可能有助于病理蛋白聚集体的稳定性，并提供一种简便的方法来触发生物技术应用的冷凝物混合。肉瘤凝结物中本质无序融合的冷形成产生亚稳态、动力学捕获的液体凝结物 (A)，可以通过热退火 (B) 将其转化为平衡液体凝结物 (C)。多种液态允许按需、刺激响应地混合冷凝物含量，以动态控制成分。
Formation of membrane‐less organelles by self‐assembly of disordered proteins can be triggered by external stimuli such as pH, salt, or temperature. These organelles, called biomolecular condensates, have traditionally been classified as liquids, gels, or solids with limited subclasses. Here, the authors show that a thermal trigger can lead to formation of at least two distinct liquid condensed phases of the fused in sarcoma low complexity (FUS LC) domain. Forming FUS LC condensates directly at low temperature leads to formation of metastable, kinetically trapped condensates that show arrested coalescence, escape from which to untrapped condensates can be achieved via thermal annealing. Using experimental and computational approaches, the authors find that molecular structure of interfacial FUS LC in kinetically trapped condensates is distinct (more β‐sheet like) compared to untrapped FUS LC condensates. Moreover, molecular motion within kinetically trapped condensates is substantially slower compared to that in untrapped condensates thereby demonstrating two unique liquid FUS condensates. Controlling condensate thermodynamic state, stability, and structure with a simple thermal switch may contribute to pathological protein aggregate stability and provides a facile method to trigger condensate mixing for biotechnology applications. Cold formation of intrinsically disordered fused in sarcoma condensates creates metastable, kinetically trapped liquid condensates (A) that can be converted into equilibrium liquid condensates (C) via thermal annealing (B). Multiple liquid states allow for on‐demand, stimuli‐responsive mixing of condensate contents to control composition dynamically.
登录
查看更多内容
影响因子：
3.7
作者：
Hawe, Andrea;Sutter, Marc;Jiskoot, Wim
通讯作者：
Jiskoot, Wim
DOI：
10.1042/bcj20160499
发表时间：
2017-04-07
期刊：
The Biochemical journal
影响因子：
--
作者：
Harrison AF;Shorter J
通讯作者：
Shorter J
影响因子：
2.5
作者：
BERJOT, M;MARX, J;ALIX, AJP
通讯作者：
ALIX, AJP
影响因子：
16.6
作者：
Gabryelczyk, Bartosz;Cai, Hao;Miserez, Ali
通讯作者：
Miserez, Ali
影响因子：
2.9
作者：
Conicella, Alexander E.;Fawzi, Nicolas L.
通讯作者：
Fawzi, Nicolas L.