Fernández-Fernández María Rosario, Valpuesta José María
Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus de la Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain.
F1000Res. 2018 Sep 19;7. doi: 10.12688/f1000research.15528.1. eCollection 2018.
Protein homeostasis (proteostasis) is an essential pillar for correct cellular function. Impairments in proteostasis are encountered both in aging and in several human disease conditions. Molecular chaperones are important players for proteostasis; in particular, heat shock protein 70 (Hsp70) has an essential role in protein folding, disaggregation, and degradation. We have recently proposed a model for Hsp70 functioning as a "multiple socket". In the model, Hsp70 provides a physical platform for the binding of client proteins, other chaperones, and cochaperones. The final fate of the client protein is dictated by the set of Hsp70 interactions that occur in a given cellular context. Obtaining structural information of the different Hsp70-based protein complexes will provide valuable knowledge to understand the functional mechanisms behind the master role of Hsp70 in proteostasis. We additionally evaluate some of the challenges for attaining high-resolution structures of such complexes.
蛋白质稳态（proteostasis）是细胞正常功能的重要支柱。在衰老过程和多种人类疾病状态中都会出现蛋白质稳态受损的情况。分子伴侣是蛋白质稳态的重要参与者；特别是热休克蛋白70（Hsp70）在蛋白质折叠、解聚和降解中起着至关重要的作用。我们最近提出了一个Hsp70作为“多插座”发挥作用的模型。在该模型中，Hsp70为客户蛋白、其他分子伴侣和共分子伴侣的结合提供了一个物理平台。客户蛋白的最终命运取决于在特定细胞环境中发生的一系列Hsp70相互作用。获取不同的基于Hsp70的蛋白质复合物的结构信息将为理解Hsp70在蛋白质稳态中的主要作用背后的功能机制提供有价值的知识。我们还评估了获得此类复合物高分辨率结构的一些挑战。
