Regulation of the Native Protein Landscape in the Nucleus by Molecular Chaperones

分子伴侣对细胞核中天然蛋白质景观的调节

• 批准号: 10437868
• 负责人: Brian C Freeman
• 金额: $ 37.69万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10437868
• 关键词: Behavior; Binding; Biological; Cell Nucleus; Cell physiology; Cells; Complex; DNA; DNA Repair; Ensure; Environment; Event; Fostering; Genetic Transcription; Genome; Homeostasis; Kinetics; Mediating; Molecular Chaperones; Monitor; Nature; Nuclear; Pathway interactions; Performance; Proteins; RNA; Regulation; Specificity; Stimulus; System; Time; Work; cofactor

ABSTRACT Homeostasis requires most, if not all, pathways to function rapidly and precisely. While cooperative interactions between proteins and cofactors helps ensure selectivity, the events mediating dynamic action are less well understood. Further complicating pathway performance is the nature of the cell interior, as it is densely packed and often contains multiple binding partners for each protein—both features increase non-productive or off-pathway interactions. These variables present great challenges for achieving homeostasis especially in the midst of fluctuating internal and external stimuli that must be monitored constantly to appropriately initiate, continue, or halt cellular processes. Hence, biological complexes must be actively and persistently disassembled in order to work on a useful time scale. We suggest that the broad binding specificity and energy-independent molecular chaperone activities of the Hsp90 chaperone system govern the kinetic behaviors of the diverse proteins within cells. Basically, Hsp90 and its cochaperones resolve inherently stable cooperative complexes into a dynamic machinery capable of rapid action that enables efficient and timely biological pathways.

摘要 稳态需要大多数（如果不是全部）途径快速而精确地发挥作用。而 蛋白质和辅因子之间的协同作用有助于确保选择性， 介导的动态行为是不太好理解。使途径性能进一步复杂化的是 细胞内部的性质，因为它是密集包装，往往含有多个结合伙伴，为每个 蛋白质-这两种特征都增加了非生产性或非途径相互作用。这些变量存在 实现内稳态的巨大挑战，特别是在内外部波动的情况下， 必须不断监测刺激以适当启动、继续或停止细胞过程。 因此，生物复合体必须积极地和持续地分解，以便在一个特定的环境中工作。 有用的时间尺度。我们认为，广泛的结合特异性和能量不依赖性的分子， Hsp 90分子伴侣系统的分子伴侣活性控制着不同分子的动力学行为。 细胞内的蛋白质。基本上，热休克蛋白90和它的辅助分子伴侣解决了固有的稳定的合作， 复杂的动态机制，能够迅速采取行动，使有效和及时的 生物途径。