title: Structure of the cathelicidin motif of protegrin-3 precursor: structural insights into the activation mechanism of an antimicrobial protein.
abstract: 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.
authors.affiliation: Centre de Biochimie Structurale, UMR CNRS 5048, UMR 554 INSERM, Université Montpellier I, 15 Avenue Charles Flahault, 34060 Montpellier Cedex, France.
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Sanchez
authors.forename: François
authors.initials: F
authors.lastname: Hoh
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Strub
authors.forename: André
authors.initials: A
authors.lastname: Aumelas
authors.forename: Christian
authors.initials: C
authors.lastname: Dumas
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; D011506:Proteins; C094881:protegrin-3