The insect antimicrobial peptide, -pyrrhocoricin, binds to and stimulates the ATPase activity of both wild-type and lidless DnaK

Abstract

Recent reports have indicated that insect antimicrobial peptides kill bacteria by inhibiting the molecular chaperone DnaK. It was proposed that the antimicrobial peptide, all-L L -pyrrhocoricin (L L -PYR), binds to two sites on DnaK, the conventional substratebinding site and the multi-helical C-terminal lid, and that inhibition of DnaK comes about from the lid mode of binding. In this report, we show using two different assays that L L -PYR binds to and stimulates the ATPase activity of both wild-type and a lidless variant of DnaK. Our study shows that L L -PYR interacts with DnaK much like the all-L L NR (NRLLLTG) peptide, which is known to bind in the conventional substrate-binding site of DnaK. L L -PYR antimicrobial activity is thus a consequence of the competitive inhibition of bacterial DnaK.

LC-MS/MS analysis of the protein profiles of escherichia coli in response to the challenge of antibacterial peptides

“…ii) self-promoted invading into the periplasmic space; iii) irreversible interaction with a hypothetical docking molecule/receptor molecule on the inner membrane (IM); iv) translocation across the membrane and into the cytoplasm of the cell; v) Binding its target most probably DnaK protein to mediate cell death (Figure 2.5) [21,24,72,[82][83][84]. However, it is possible that these peptides kill bacteria by other mechanisms not yet identified.…”