Chaperone protein DnaK (DnaK) (DnaK)

Chaperone protein DnaK is the primary bacterial homolog of the eukaryotic 70 kDa heat shock protein (Hsp70) and serves as a central hub in the bacterial molecular chaperone network [6, 7]. It plays a critical role in protein homeostasis by facilitating the folding of nascent polypeptides, refolding misfolded proteins, and solubilizing protein aggregates, particularly under stress conditions such as heat shock or antibiotic exposure [1, 8, 11]. DnaK functions through an ATP-dependent cycle of substrate binding and release, regulated by co-chaperones DnaJ and the nucleotide exchange factor GrpE [3, 5, 9]. Beyond its role in proteostasis, DnaK is essential for bacterial virulence, biofilm formation, and the development of multi-drug resistance in various pathogens [3, 6, 7, 9]. Interestingly, certain bacterial DnaK proteins, such as those from Mycoplasma, have been implicated in oncogenesis by interfering with the p53 tumor suppressor pathway in host cells [4, 16]. As a therapeutic target, DnaK is being targeted by novel proline-rich antimicrobial peptides (PrAMPs) like Api88 and ARV-1502, which selectively inhibit its activity without affecting human Hsp70, as well as small molecule allosteric inhibitors [6, 10, 13, 16].

Other names

Hsp70 homolog70 kDa heat shock proteinProkaryotic Hsp70Heat shock protein 70

Inhibition of ATPase activity, prevention of chaperone-assisted protein folding, and disruption of co-chaperone interactions.