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New insights on human Hsp70-escort protein 1: Chaperone exercise, interplay with liposomes, mobile localizations and HSPA’s self-assemblies transforming

This article was originally published here

Int J Biol Macromol. 2021, April 12: S0141-8130 (21) 00813-8. doi: 10.1016 / j.ijbiomac.2021.04.048. Online before printing.


The 70 kDa heat shock proteins (Hsp70) tend to self-assemble under thermal stress conditions and form supramolecular assemblies (SMA), which can have a detrimental effect on the viability of cells. In mitochondria, the cochaperone Hsp70 escort protein 1 (Hep1) keeps the mitochondrial Hsp70 (mtHsp70) in a soluble and functional state and thus contributes to maintaining proteostasis. Here we examined the interaction between human Hep1 (hHep1) and HSPA9 (human mtHsp70) or HSPA1A (Hsp70-1A) in monomeric and thermal SMA states to get more information about the mechanisms involved. hHep1 was able to block the formation of HSPA-SMAs under thermal treatment and to stimulate HSPA-ATPase activity in both monomeric and preformed SMA. The interaction of hHep1 with both monomeric and SMA HSPAs showed a stoichiometric ratio close to 1, suggesting that hHep1 has access to most of the protomers within the SMA. Interestingly, hHep1 has remodeled HSPA9 and HSPA1A SMAs into smaller forms. In addition, hHep1 was detected in the mitochondria and in the nucleus of cells transfected with the respective coding DNA and interacted with liposomes that resemble mitochondrial membranes. Overall, these new functions reinforce the fact that hHep1 acts as a “chaperone for a chaperone”, which can play a decisive role in cellular proteostasis.

PMID: 33857516 | DOI: 10.1016 / j.ijbiomac.2021.04.048