IF 40.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jinying Gu, Yanyi He, Chenxi He, Qiuyue Zhang, Qifei Huang, Shangjun Bai, Ruoning Wang, Qidong You, Lei Wang
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引用次数: 0

摘要

分子伴侣是一类复杂的客户调节系统,在防止蛋白质错误折叠和异常聚集、调节蛋白质平衡以及在不断变化的环境条件下保护细胞免受损伤等方面发挥着重要作用。随着人们对分子伴侣生物学机制认识的加深,它们与疾病发生和发展之间的联系表明,这些蛋白质是有希望的治疗干预靶标,从而引起了人们的广泛兴趣。在此,我们回顾了在确定分子伴侣和热休克蛋白 90(HSP90)伴侣系统复合物结构方面的最新进展。我们还描述了分子伴侣的特征,并揭示了分子伴侣循环中通过与各种辅助伴侣相互作用而运行的复杂调控机制。此外,我们还深入分析了分子伴侣如何通过调节致病蛋白来影响疾病。此外,我们还以分子伴侣为重点,系统地讨论了近期的临床进展和临床前阶段的各种药物设计策略。最近的研究发现了多种针对分子伴侣系统的新型调控策略,其化合物的作用机制与传统抑制剂不同。因此,随着更多新型设计策略的开发,以分子伴侣为靶点将极大地促进潜在新药的发现。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Advances in the structures, mechanisms and targeting of molecular chaperones

Advances in the structures, mechanisms and targeting of molecular chaperones

Molecular chaperones, a class of complex client regulatory systems, play significant roles in the prevention of protein misfolding and abnormal aggregation, the modulation of protein homeostasis, and the protection of cells from damage under constantly changing environmental conditions. As the understanding of the biological mechanisms of molecular chaperones has increased, their link with the occurrence and progression of disease has suggested that these proteins are promising targets for therapeutic intervention, drawing intensive interest. Here, we review recent advances in determining the structures of molecular chaperones and heat shock protein 90 (HSP90) chaperone system complexes. We also describe the features of molecular chaperones and shed light on the complicated regulatory mechanism that operates through interactions with various co-chaperones in molecular chaperone cycles. In addition, how molecular chaperones affect diseases by regulating pathogenic proteins has been thoroughly analyzed. Furthermore, we focus on molecular chaperones to systematically discuss recent clinical advances and various drug design strategies in the preclinical stage. Recent studies have identified a variety of novel regulatory strategies targeting molecular chaperone systems with compounds that act through different mechanisms from those of traditional inhibitors. Therefore, as more novel design strategies are developed, targeting molecular chaperones will significantly contribute to the discovery of new potential drugs.

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来源期刊
Signal Transduction and Targeted Therapy
Signal Transduction and Targeted Therapy Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
44.50
自引率
1.50%
发文量
384
审稿时长
5 weeks
期刊介绍: Signal Transduction and Targeted Therapy is an open access journal that focuses on timely publication of cutting-edge discoveries and advancements in basic science and clinical research related to signal transduction and targeted therapy. Scope: The journal covers research on major human diseases, including, but not limited to: Cancer,Cardiovascular diseases,Autoimmune diseases,Nervous system diseases.
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