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: 10641829
• 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/10641829
• 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 动态平衡需要大部分(如果不是全部)途径才能快速而准确地发挥作用。而当 蛋白质和辅因子之间的协同作用有助于确保选择性，事件 人们对调解动态行为知之甚少。使路径性能进一步复杂化的是 细胞内部的性质，因为它是密集排列的，通常每个细胞都有多个结合配对 蛋白质-这两种功能都会增加非生产性或非途径的相互作用。这些变数存在 实现动态平衡的巨大挑战，特别是在内外波动的情况下 必须持续监测以适当地启动、继续或停止细胞过程的刺激。 因此，生物复合体必须被积极和持久地分解，才能在 有用的时标。我们认为，广泛的结合特异性和能量无关的分子 Hsp90分子伴侣系统的分子伴侣活动支配着不同种类的 细胞内的蛋白质。基本上，Hsp90和它的伴侣解决了本质上稳定的合作 成为一种动态的机器，能够快速行动，从而能够高效和及时地 生物途径。

项目成果

Protocol for establishing a protein interactome based on close physical proximity to a target protein within live budding yeast.

• DOI: 10.1016/j.xpro.2023.102663
• 发表时间: 2023-12-15
• 期刊: STAR PROTOCOLS
• 作者: Kolhe, Janhavi A;Babu, Neethu L;Freeman, Brian C
• 通讯作者: Freeman, Brian C

Regulation of Protein Transport Pathways by the Cytosolic Hsp90s.

• DOI: 10.3390/biom12081077
• 发表时间: 2022-08-05
• 期刊: Biomolecules
• 影响因子: 5.5

Genome Organization and Dynamics Specialty Grand Challenge.

• DOI: 10.3389/fmolb.2021.818707
• 发表时间: 2021
• 期刊: Frontiers in molecular biosciences
• 影响因子: 5
• 作者: Freeman BC

Inhibiting U1 telescripting: A means to an end for transcription.

• DOI: 10.1016/j.molcel.2022.04.001
• 发表时间: 2022-04-21
• 期刊: MOLECULAR CELL
• 影响因子: 16
• 作者: Peng, Audrey Yi Tyan;Freeman, Brian C.
• 通讯作者: Freeman, Brian C.

Genome organization: Tag it, move it, place it.

• DOI: 10.1016/j.ceb.2020.10.005
• 发表时间: 2021-03
• 期刊: Current opinion in cell biology
• 影响因子: 7.5
• 作者: Peng AYT;Kolhe JA;Behrens LD;Freeman BC
• 通讯作者: Freeman BC