SOLUTION STRUCTURE OF PROTEGRIN-1, A BROAD-SPECTRUM ANTIMICROBIAL PEPTIDE FROM PORCINE LEUKOCYTES

Background: The protegrins are a family of arginine- and cysteine-rich cationic peptides found in porcine leukocytes that exhibit a broad ra nge of antimicrobial and antiviral activities. They are composed of 16 -18 amino-acid residues including four cysteines, which form two disul fide linkages. To begin to understand the mechanism of action of these peptides, we set out to determine the structure of protegrin-1 (PG-1) . Results: We used two-dimensional homonuclear nuclear magnetic resona nce spectroscopy to study the conformation of both natural and synthet ic PG-1 under several conditions. A refined three-dimensional structur e of synthetic PG-1 is presented. Conclusions: Both synthetic and natu ral protegrin-1 form a well-defined structure in solution composed pri marily of a two-stranded antiparallel beta sheet, with strands connect ed by a beta turn. The structure of PG-1 suggests ways in which the pe ptide may interact with itself or other molecules to form the membrane pores and the large membrane-associated assemblages observed in prote grin-treated, gram-negative bacteria.