Protease processing of misfolded His 6 -proHNP1 NE, PR3, and CG degraded proHNP1B, the misfolded form of the HNP1 precursor. In contrast to the discrete products generated by digestion of proHNP1A by the serine proteases ( Fig. 5) , NE, PR3, or CG treatment of proHNP1B yielded no mature HNP1 or HNP1 derivatives in the digestion mixtures detectable by C18 RP-HPLC or MALDI-TOF MS (data not shown). These results indicate that the correct fold and disulfide linkages in proHNP1 are required for processing of the precursor to mature peptide and to confer resistance to these activating convertases.