In vitro cleavage and activation of
proRMAD-4(20–94) by NE, CG, and P3. In A,
samples of proRMAD-4(20–94) (10 μg) were incubated
overnight in vitro with (+) or without (–) NE, CG, and P3, and
digests were resolved by AU-PAGE and stained with Coomassie Blue (see
“Experimental Procedures”). proRMAD-4(20–94) is
digested by NE, and the digested product runs alongside native
RMAD-4(62–94). CG and P3 digest
proRMAD-4(20–94), and the products have lower mobilities in
AU-PAGE analysis. In B, bactericidal activities against S.
typhimurium ΔphoP of recombinant
proRMAD-4(20–94), RMAD-4(62–94), and the
complete digests of proRMAD-4(20–94) incubated with each of
the azurophil granule serine proteases. Panels A, peptides exposed to
NE; B, peptides exposed to CG; C, peptides exposed to P3.
Symbols:(-▾-), proRMAD-4(20–94) with no serine
protease; (-○-), proRMAD-4(20–94) with serine protease;
(-▿-), RMAD-4(62–94) with no serine protease;
(-•-), RMAD-4(62–94) exposed to serine protease.
proRMAD-4(20–94) lacks bactericidal activity, native
RMAD-4(62–94) is bactericidal. The three serine proteases
convert inactive proRMAD-4(20–94) to a bactericidal
molecule.