title: Conformational study of bovine lactoferricin in membrane-micking conditions by molecular dynamics simulation and circular dichroism.
abstract: Lactoferricins are potent antimicrobial peptides released by pepsin cleavage of Lactoferrins. Bovine Lactoferricin (LfcinB) has higher activity than the intact bovine Lactoferrin, and is the most active among the other Lactoferricins of human, murine and caprine origin. In the intact protein the fragment corresponding to LfcinB is in an helical conformation, while in water LfcinB adopts an amphipathic β-hairpin structure. However, whether any of these structural motifs is the antibacterial active conformation, i.e., the one interacting with bacterial membrane components, remains to be seen. Here we present Circular Dichroism (CD) spectra and Molecular Dynamics (MD) simulations indicating that in membrane-mimicking solvents the LfcinB adopts an amphipathic β-hairpin structure similar to that observed in water, but differing in the dynamic behavior of the side-chains of the two tryptophan residues. In the membrane-mimicking solvent these side-chains show a high propensity to point towards the hydrophobic environment, rather than being in the hydrophobic core as seen in water, while the backbone preserves the hairpin conformation as found in water. These results suggest that the tryptophans might act as anchors pulling the stable, solvent-invariant hairpin structure into the membrane.
authors.affiliation: Department of Chemistry, Chemical Engineering and Materials, University of L'Aquila, via Vetoio (Coppito 1), 67010, Coppito, AQ, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Daidone
authors.forename: Alessandro
authors.initials: A
authors.lastname: Magliano
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Nola
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Mignogna
authors.forename: Matilda Manuela
authors.initials: MM
authors.lastname: Clarkson
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Lizzi
authors.forename: Arduino
authors.initials: A
authors.lastname: Oratore
authors.forename: Fernando
authors.initials: F
authors.lastname: Mazza
mesh_terms: D000818:Animals; D002417:Cattle; D002942:Circular Dichroism / Q000379:methods*; D007781:Lactoferrin / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D017433:Protein Structure, Secondary
chemical_list: C082171:lactoferricin B; D007781:Lactoferrin