The Central Kink Region of Fowlicidin-2, an α-Helical Host Defense Peptide, Is Critically Involved in Bacterial Killing and Endotoxin Neutralization
| Autor: | Yugendar R. Bommineni, Jose L. Soulages, Yanjing Xiao, Om Prakash, Alvaro I. Herrera, Guolong Zhang |
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| Rok vydání: | 2008 |
| Předmět: |
Erythrocytes
medicine.medical_treatment Molecular Sequence Data Antimicrobial peptides Peptide Microbial Sensitivity Tests Biology Gram-Positive Bacteria Hemolysis Neutralization Cathelicidin Microbiology Structure-Activity Relationship Gram-Negative Bacteria medicine Animals Humans Immunology and Allergy Structure–activity relationship Amino Acid Sequence Nuclear Magnetic Resonance Biomolecular Peptide sequence chemistry.chemical_classification Innate immune system Circular Dichroism Immunity Innate Endotoxins Cathelicidins Biochemistry chemistry lipids (amino acids peptides and proteins) Caco-2 Cells Antimicrobial Cationic Peptides Research Article |
| Zdroj: | J Innate Immun |
| ISSN: | 1662-8128 1662-811X |
| DOI: | 10.1159/000174822 |
| Popis: | Fowlicidins are a group of newly identified chicken cathelicidin host defense peptides. We have shown that the putatively mature fowlicidin-2 of 31 amino acid residues possesses potent antibacterial and lipopolysaccharide (LPS)- neutralizing activities, but with a noticeable toxicity to mammalian cells. As a first step in exploring the structure-activity relationships of fowlicidin-2, in this study we determined its tertiary structure by nuclear magnetic resonance spectroscopy. Unlike the majority of cathelicidins, which are composed of a predominant alpha-helix with a short hinge sequence near the center, fowlicidin-2 consists of 2 well-defined alpha-helical segments (residues 6-12 and 23-27) connected by a long extensive kink (residues 13-20) induced by proline. To further investigate the functional significance of each of these structural components, several N- and C-terminal deletion analogs of fowlicidin-2 were synthesized and analyzed for their antibacterial, cytotoxic and LPS-neutralizing activities. Our results indicated that neither the N- nor C-terminal alpha-helix alone is sufficient to confer any function. Rather, fowlicidin-2(1-18) and fowlicidin-2(15-31), 2 alpha-helical segments with inclusion of the central cationic kink region, retained substantial capacities to kill bacteria and neutralize the LPS-induced proinflammatory response, relative to the parent peptide. More desirably, these 2 peptide analogs showed substantially reduced toxicity to human erythrocytes and epithelial cells, indicative of improved potential as antibacterial and antisepsis agents. To our knowledge, fowlicidin-2 is the first alpha-helical cathelicidin, with the central kink region shown to be critically important in killing bacteria and neutralizing LPS. |
| Databáze: | OpenAIRE |
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