Chaperone protein DnaK (DnaK)

Chaperone protein DnaK is the primary bacterial representative of the Hsp70 family, serving as a central hub in the protein folding machinery (UniProt P0A6Y8). It facilitates the folding of newly synthesized proteins, prevents the aggregation of misfolded proteins, and assists in the translocation of proteins across membranes (PMID: 28836138). The functional cycle of DnaK is tightly regulated by its co-chaperones, DnaJ and GrpE, which modulate its ATP-bound and ADP-bound states to control substrate affinity (PMID: 31434151). In the context of infection, DnaK is crucial for bacterial survival under the stressful conditions of the host environment, such as high temperature and oxidative stress, and is often linked to the expression of virulence factors (PMID: 25613164). As a therapeutic target, DnaK is inhibited by various proline-rich antimicrobial peptides (PrAMPs) like apidaecin and oncocin, which bind to its substrate-binding pocket and stall the chaperone cycle (PMID: 21664394). This inhibition leads to the accumulation of misfolded proteins and eventual bacterial cell death, making it a high-priority target for addressing multi-drug resistant bacterial pathogens (PMID: 17506534).

Other names

70 kDa heat shock proteinHsp70 homologDnaK proteinHeat shock protein 70

Inhibition of the chaperone cycle by binding to the substrate-binding domain, preventing protein refolding and causing lethal protein aggregation (PMID: 21664394, 31434151).