Structure of the cathelicidin motif of protegrin-3 precursor: structural insights into the activation mechanism of an antimicrobial protein.
Cathelicidins are a family of antimicrobial proteins isolated from leucocytes and epithelia cells that contribute to the innate host defense mechanisms in mammalians. Located in the C-terminal part of the holoprotein, the cathelicidin-derived antimicrobial peptide is liberated by a specific protease cleavage. Here, we report the X-ray structure of the cathelicidin motif of protegrin-3 solved by MAD phasing using the selenocysteine-labeled protein. Its overall structure represents a fold homologous to the cystatin family and adopts two native states, a monomer, and a domain-swapped dimer. This crystal structure is the first example of a structural characterization of the highly conserved cathelicidin motif and thus provides insights into the possible mechanism of activation of the antimicrobial protegrin peptide.
Sanchez
Jean-Frédéric
JF
Centre de Biochimie Structurale, UMR CNRS 5048, UMR 554 INSERM, Université Montpellier I, 15 Avenue Charles Flahault, 34060 Montpellier Cedex, France.
Hoh
François
F
Strub
Marie-Paule
MP
Aumelas
André
A
Dumas
Christian
C
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides; D018360:Crystallography, X-Ray; D019281:Dimerization; D008969:Molecular Sequence Data; D010455:Peptides; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; D011506:Proteins; C094881:protegrin-3