The physiological regulation mechanism of gsp70 is revealed

As a reversible redox modification, glutathione modification on protein cysteine Cys can protect protein from irreversible oxidative damage such as sulfonation, on the other hand, it plays a signal transduction function and transmits redox signal like phosphorylation modification. Hsp70 is the core molecular chaperone in protein quality control system, which is of great significance for the homeostasis of life. Except for a few HSP70, most HSP70 have at least one Cys. Further exploring the redox modification mechanism of Hsp70 is of great significance to help reveal the redox regulation mechanism of protein homeostasis and expand the understanding of HSP70 function.

recently, cosa research group and Chen Chang research team of Institute of Biophysics, Chinese Academy of Sciences, found that glutathione modification of two cysteine on the α helix cap of C-terminal substrate binding domain of human stress-induced HSP70 led to unfolding of its C-terminal α helix cap, thus exposing leu542. The interaction between the residue and the substrate binding domain led to Hsp70 This process is completely reversible with the occurrence of desglutathionation. The results reveal the regulation mechanism of GSH modification on the structure and function of HSP70, and clarify that GSH modification on the C-terminal domain of Hsp70 is a new mechanism to regulate the binding capacity of HSP70 substrate, which may regulate the activity of its substrate during oxidative stress, thus transmitting redox signals.

glutathione modification of cysteine on the C-terminal α – helix cap of human stress-induced HSP70 will result in unfolding of α – helix cap, and leu542 occupies its own substrate binding site. The process is completely reversible. After the substrate binding site was blocked by leu542, HSP70 released substrates, including signal molecules related to oxidative stress, such as heat shock transcription factor and HSF1. After the release of signal molecules, the next step of stress process will be started. Focus