Structural aspects and biological properties of the cathelicidin PMAP‐36

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Abstract
PMAP-36 is a cathelicidin-derived host defence peptide originally deduced by a transcript from pig bone marrow RNA. The expression of the propeptide in leukocytes, and the structure, antimicrobial activity, and mechanism of action of the mature peptide were investigated. The proform is stored as a dimeric precursor of 38 kDa formed by a dimerization site at its C-terminal cysteine residue; it is likely that the mature peptide is dimeric when released. Monomeric and dimeric forms of PMAP-36 were chemically synthesized and their activity compared. Both forms assumed an amphipathic alpha-helical conformation and exhibited a potent and rapid microbicidal activity against a wide spectrum of microorganisms, mediated by their ability to permeabilize the microbial membranes rapidly. A shortened fragment localized the helical region to the N terminus, but showed a significantly lower potency and slower permeabilization kinetics, indicating an important role of the nonhelical C-terminal hydrophobic portion of this molecule. Dimerization modulated the effectiveness of the peptide in terms of killing and permeabilization kinetics, and reduced medium dependence. It allows the molecule to achieve an impressive charge density (+28 in 70 residues), although the significance of this feature with respect to biological activity has yet to be determined.