人类 HSP90α 中的 F352A 和 Y528A 突变会减少纤维粘连蛋白的结合以及细胞衍生基质中的纤维生成。

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Cell Stress & Chaperones Pub Date : 2023-11-01 Epub Date: 2023-06-23 DOI:10.1007/s12192-023-01362-9
Abir Chakraborty, Ronald Tonui, Adrienne Lesley Edkins
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引用次数: 0

摘要

HSP90 是一种普遍表达的伴侣蛋白,它能调节许多被称为 "客户 "的底物蛋白的成熟。糖蛋白纤连蛋白(FN)是细胞外基质(ECM)的重要蛋白质,也是 HSP90 的客户蛋白。FN 和 HSP90 直接相互作用,FN 的 ECM 受外源 HSP90 或 HSP90 抑制剂的调节。在此,我们扩展了对 HSP90 - FN 相互作用的分析。通过 HSP90 与化脓性链球菌 F1 粘附蛋白的功能上游结构域(FUD)之间对 FN 结合的竞争,证明了纤连蛋白(FN70)N 端 70 kDa 片段和 FN I 型重复的重要性。此外,His-HSP90α突变 F352A 和 Y528A(单独或组合)降低了与体外全长 FN(FN-FL)和 FN70 的结合。与野生型 His-HSP90α 不同的是,在 Hs578T 细胞系模型中,外源添加这些 HSP90 突变体并不会增强 FN 基质的组装。有趣的是,HSP90 E353A突变在体外并没有显著降低HSP90与FN的相互作用,但在Hs578T细胞衍生基质中却极大地阻碍了FN基质的组装。综上所述,这些数据扩展了我们对 HSP90 在 FN 成纤过程中作用的理解,并表明 HSP90 对 FN ECM 组装的促进作用并不完全受 HSP90 与 FN 之间直接相互作用亲和力的调节。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Mutations F352A and Y528A in human HSP90α reduce fibronectin association and fibrillogenesis in cell-derived matrices.

Mutations F352A and Y528A in human HSP90α reduce fibronectin association and fibrillogenesis in cell-derived matrices.

HSP90 is a ubiquitously expressed chaperone protein that regulates the maturation of numerous substrate proteins called 'clients'. The glycoprotein fibronectin (FN) is an important protein of the extracellular matrix (ECM) and a client protein of HSP90. FN and HSP90 interact directly, and the FN ECM is regulated by exogenous HSP90 or HSP90 inhibitors. Here, we extend the analysis of the HSP90 - FN interaction. The importance of the N-terminal 70-kDa fragment of fibronectin (FN70) and FN type I repeat was demonstrated by competition for FN binding between HSP90 and the functional upstream domain (FUD) of the Streptococcus pyogenes F1 adhesin protein. Furthermore, His-HSP90α mutations F352A and Y528A (alone and in combination) reduced the association with full-length FN (FN-FL) and FN70 in vitro. Unlike wild type His-HSP90α, these HSP90 mutants did not enhance FN matrix assembly in the Hs578T cell line model when added exogenously. Interestingly, the HSP90 E353A mutation, which did not significantly reduce the HSP90 - FN interaction in vitro, dramatically blocked FN matrix assembly in Hs578T cell-derived matrices. Taken together, these data extend our understanding of the role of HSP90 in FN fibrillogenesis and suggest that promotion of FN ECM assembly by HSP90 is not solely regulated by the affinity of the direct interaction between HSP90 and FN.

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来源期刊
Cell Stress & Chaperones
Cell Stress & Chaperones 生物-细胞生物学
CiteScore
7.60
自引率
2.60%
发文量
59
审稿时长
6-12 weeks
期刊介绍: Cell Stress and Chaperones is an integrative journal that bridges the gap between laboratory model systems and natural populations. The journal captures the eclectic spirit of the cellular stress response field in a single, concentrated source of current information. Major emphasis is placed on the effects of climate change on individual species in the natural environment and their capacity to adapt. This emphasis expands our focus on stress biology and medicine by linking climate change effects to research on cellular stress responses of animals, micro-organisms and plants.
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