3-DIMENSIONAL SOLUTION STRUCTURE OF LACTOFERRICIN-B, AN ANTIMICROBIALPEPTIDE DERIVED FROM BOVINE LACTOFERRIN

The solution structure of bovine lactoferricin (LfcinB) has been deter mined using 2D H-1 NMR spectroscopy, LfcinB is a 25-residue antimicrob ial peptide released by pepsin cleavage of lactoferrin, an 80 kDa iron -binding glycoprotein with many immunologically important functions. T he NMR structure of LfcinB reveals a somewhat distorted antiparallel b eta-sheet. This contrasts with the X-ray structure of bovine lactoferr in, in which residues 1-13 (of LfcinB) form an alpha-helix. Hence, thi s region of lactoferricin B appears able to adopt a helical or sheetli ke conformation, similar to what has been proposed for the amyloidogen ic prion proteins and Alzheimer's beta-peptides. LfcinB has an extende d hydrophobic surface comprised of residues Phe1, Cys3, Trp6, Trp8, Pr o16, Ile18, and Cys20. The side chains of these residues are well-defi ned in the NMR structure. Many hydrophilic and positively charged resi dues surround the hydrophobic surface, giving LfcinB an amphipathic ch aracter, LfcinB bears numerous similarities to a vast number of cation ic peptides which exert their antimicrobial activities through membran e disruption. The structures of many of these peptides have been well characterized, and models of their membrane-permeabilizing mechanisms have been proposed. The NMR solution structure of LfcinB may be more r elevant to membrane interaction than that suggested by the X-ray struc ture of intact lactoferrin. Based on the solution structure, it is now possible to propose potential mechanisms for the antimicrobial action of LfcinB.