Silbermann Laura-Marie, Vermeer Benjamin, Schmid Sonja, Tych Katarzyna
Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, Netherlands.
Laboratory of Biophysics, Wageningen University & Research, Wageningen, Netherlands.
Elife. 2024 Dec 31;13:e102666. doi: 10.7554/eLife.102666.
Molecular chaperones are vital proteins that maintain protein homeostasis by assisting in protein folding, activation, degradation, and stress protection. Among them, heat-shock protein 90 (Hsp90) stands out as an essential proteostasis hub in eukaryotes, chaperoning hundreds of 'clients' (substrates). After decades of research, several 'known unknowns' about the molecular function of Hsp90 remain unanswered, hampering rational drug design for the treatment of cancers, neurodegenerative, and other diseases. We highlight three fundamental open questions, reviewing the current state of the field for each, and discuss new opportunities, including single-molecule technologies, to answer the known unknowns of the Hsp90 chaperone.
分子伴侣是一类重要的蛋白质，它们通过协助蛋白质折叠、激活、降解和应激保护来维持蛋白质稳态。其中，热休克蛋白90（Hsp90）在真核生物中作为一个至关重要的蛋白质稳态中心脱颖而出，陪伴着数百种“客户”（底物）。经过数十年的研究，关于Hsp90分子功能的几个“已知的未知问题”仍未得到解答，这阻碍了针对癌症、神经退行性疾病和其他疾病的合理药物设计。我们着重介绍三个基本的开放性问题，回顾该领域针对每个问题的当前状态，并讨论新的机遇，包括单分子技术，以解答Hsp90分子伴侣的已知未知问题。
Zotero 插件
