Mechanism of the HSP70 Activation by J-Domain Binding

The heat shock 70-kDa proteins (HSP70) are the most ubiquitous and important chaperones that function in many biological events including protein folding and assembly, post-translational modification, transportation and secretion, and degradation. The J domain-containing co-chaperones are required for regulating the ATPase activity of HSP70 and subsequently modulating the substrate binding and ATPase cycle, but the mechanism underlying the J-domain mediated HSP70 function remains elusive.

 

GAO Xuechao and her colleagues, led by Prof. HU Hongyu from Shanghai Institute of Biochemistry and Cell Biology, SIBS, CAS, have revealed the dual function of HSJ1a, a J domain co-chaperone, in the regulation of substrate degradation (PLoS ONE, 6, e19763, 2011). Based on this study, they applied biochemical and NMR strategies to study the interaction between human inducible HSP70 and the J domain of HSJ1a. They found that the J domain of HSJ1a shares a conserved structure with other J domains from both eukaryotic and prokaryotic species, and it mediates the interaction with the ATPase cycle of HSP70. Their in vitro study corroborates that the N-terminus of HSP70 including the ATPase domain and the substrate-binding β-subdomain is not sufficient to bind with the J domain of HSJ1a. The C-terminal helical α-subdomain of HSP70, which was considered to function as a lid of the substrate-binding domain, is crucial for binding with the J domain of HSJ1a and stimulating the ATPase activity of HSP70. These fluctuating helices are likely to contribute to a proper conformation of HSP70 for J-domain binding other than to directly bind with the J domain. Their findings provide an alternative mechanism of allosteric activation for functional regulation of HSP70 by its J-domain co-chaperones.

 

This work entitled “The C-terminal Helices of Heat Shock Protein 70 Are Essential for J-domain Binding and ATPase Activation” was published in The Journal of Biological Chemistry on February 17^th, 2011.

 

This study was supported by the grants from the Chinese Academy of Sciences, the Ministry of Science and Technology, and the National Natural Science Foundation of China. (SIBCB)

 

AUTHOR CONTACT:

HU Hongyu

Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

Phone:86-21-54921121; E-mail: hyhu@sibs.ac.cn