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Initial Insights into Structure-Activity Relationships of Avian Defensins*
- Source :
- Journal of Biological Chemistry, Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2012, 287 (10), pp.7746-55. ⟨10.1074/jbc.M111.312108⟩, Journal of Biological Chemistry 10 (287), 7746-7755. (2012), Journal of Biological Chemistry; (2011)
- Publication Year :
- 2011
- Publisher :
- American Society for Biochemistry and Molecular Biology, 2011.
-
Abstract
- Data Supplement: Supplemental Figures & Table ; International audience; Numerous β-defensins have been identified in birds, and the potential use of these peptides as alternatives to antibiotics has been proposed, in particular to fight antibiotic-resistant and zoonotic bacterial species. Little is known about the mechanism of antibacterial activity of avian β-defensins, and this study was carried out to obtain initial insights into the involvement of structural features or specific residues in the antimicrobial activity of chicken AvBD2. Chicken AvBD2 and its enantiomeric counterpart were chemically synthesized. Peptide elongation and oxidative folding were both optimized. The similar antimicrobial activity measured for both L- and D-proteins clearly indicates that there is no chiral partner. Therefore, the bacterial membrane is in all likelihood the primary target. Moreover, this work indicates that the three-dimensional fold is required for an optimal antimicrobial activity, in particular for gram-positive bacterial strains. The three-dimensional NMR structure of chicken AvBD2 defensin displays the structural three-stranded antiparallel β-sheet characteristic of β-defensins. The surface of the molecule does not display any amphipathic character. In light of this new structure and of the king penguin AvBD103b defensin structure, the consensus sequence of the avian β-defensin family was analyzed. Well conserved residues were highlighted, and the potential strategic role of the lysine 31 residue of AvBD2 was emphasized. The synthetic AvBD2-K31A variant displayed substantial N-terminal structural modifications and a dramatic decrease in activity. Taken together, these results demonstrate the structural as well as the functional role of the critical lysine 31 residue in antimicrobial activity.
- Subjects :
- MECHANISM
Magnetic Resonance Spectroscopy
beta-Defensins
APIDAECIN
MESH: Protein Structure, Secondary
peptide antimicrobien
Biochemistry
Protein Structure, Secondary
MESH: Gram-Positive Bacteria
Protein structure
MESH: Structure-Activity Relationship
MESH: Avian Proteins
spectrométrie de masse
MESH: Animals
Defensin
0303 health sciences
integumentary system
Oxidative folding
MESH: Chickens
respiratory system
Antimicrobial
ESCHERICHIA-COLI
BACTERIA
Protein Structure and Folding
défensine aviaire
activité antimicrobienne
animal structures
Antimicrobial peptides
poulet
Biology
Gram-Positive Bacteria
SEQUENCE
Microbiology in the medical area
Avian Proteins
03 medical and health sciences
MAMMALIAN DEFENSINS
Structure-Activity Relationship
Consensus sequence
Structure–activity relationship
Animals
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Molecular Biology
030304 developmental biology
030306 microbiology
MESH: Magnetic Resonance Spectroscopy
fungi
Cell Membrane
Cell Biology
biochemical phenomena, metabolism, and nutrition
ANTIMICROBIAL PEPTIDES
PREVENTION
MESH: beta-Defensins
volaille
Beta defensin
INTEGRAL MEMBRANE-PROTEINS
immunité
Chickens
MESH: Cell Membrane
Subjects
Details
- Language :
- English
- ISSN :
- 00219258 and 1083351X
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry, Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2012, 287 (10), pp.7746-55. ⟨10.1074/jbc.M111.312108⟩, Journal of Biological Chemistry 10 (287), 7746-7755. (2012), Journal of Biological Chemistry; (2011)
- Accession number :
- edsair.doi.dedup.....e0b15aad9c73f46724ba96b72f9700fd