Hsp70是保守的生命活动必需分子伴侣，一方面参与多种细胞活动，另一方面是细胞活动的缓冲蛋白。Hsp70具有一定的动态性，受核苷酸和多肽结合的变构调节，这些构成其功能循环的基础，Hsp70的变构调节是深入探讨Hsp70作用机制的焦点问题，获得了广泛的关注和研究。多年来保守性相对较差的Hsp70的底物结合域的α螺旋盖子结构（SBDα）的研究仍相对较少，缺乏深入，近年来的研究已经提示该结构域对于Hsp70的功能和变构调节具有重要意义。本项目将致力于研究不同Hsp70的特异性的SBDα对Hsp70的底物结合等功能的影响，以及对Hsp70和辅分子伴侣相互作用的影响，研究SBDα和Hsp70其他结构域相互作用的详细机制，探索SBDα在Hsp70的变构调节中的重要意义。本项目成果将为Hsp70功能调节的机制研究提供新思路，为已有的Hsp70的变构调节机制提供新的视角。

Hsp70 is a conserved molecular chaperone which is essential for life due to its participation in a wide range of cellular activities and its role in protein homeostasis. Dynamics and allosteric regulation by nucleotide and peptide is the basis for the functional cycle of Hsp70. Understanding the allosteric regulation mechanism of Hsp70 is a key problem that has been studied in depth. Although recent studies have indicated its substrate binding domain alpha-helical lid structure (SBDα) is important for function and allosteric regulation of Hsp70, the contribution of the relatively poorly conserved SBDα is a neglected aspect of the research carried out to date. This study will focus on the effect of specific SBDα sequences from different Hsp70 family members on the function of Hsp70, such as substrate binding, and the effect on interaction between Hsp70 and its co-chaperones. This study will also address the mechanistic details of how the SBDα interacts with the other domains of Hsp70 and probe significance of the SBDα in regulating allostery of Hsp70. This project will provide new insight into Hsp70 function and the mechanism of its allosteric regulation.