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 range of antimicrobial and antiviral activities. They are composed of 16-18 amino-acid residues including four cysteines, which form two disulfide 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 resonance spectroscopy to study the conformation of both natural and synthetic PG-1 under several conditions. A refined three-dimensional structure of synthetic PG-1 is presented.


CONCLUSIONS
Both synthetic and natural protegrin-1 form a well-defined structure in solution composed primarily of a two-stranded antiparallel beta sheet, with strands connected by a beta turn. The structure of PG-1 suggests ways in which the peptide may interact with itself or other molecules to form the membrane pores and the large membrane-associated assemblages observed in protegrin-treated, gram-negative bacteria.
Fahrner
R L
RL
Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA. feigon@ewald.mbi.ucla.edu
Dieckmann
T
T
Harwig
S S
SS
Lehrer
R I
RI
Eisenberg
D
D
Feigon
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification; D023181:Antimicrobial Cationic Peptides; D007962:Leukocytes / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D012996:Solutions; D013552:Swine
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D011506:Proteins; D012996:Solutions; C094880:protegrin-1