NR AFTI

AU Hwang,P.M.; Zhou,N.; Shan,X.; Arrowsmith,C.H.; Vogel,H.J.

TI Three-dimensional solution structure of lactoferricin B, an antimicrobial peptide derived from bovine lactoferrin

QU Biochemistry 1998 Mar 24; 37(12): 4288-98

PT journal article

AB The solution structure of bovine lactoferricin (LfcinB) has been determined using 2D 1H NMR spectroscopy. LfcinB is a 25-residue antimicrobial peptide released by pepsin cleavage of lactoferrin, an 80 kDa iron-binding glycoprotein with many immunologically important functions. The NMR structure of LfcinB reveals a somewhat distorted antiparallel beta-sheet. This contrasts with the X-ray structure of bovine lactoferrin, in which residues 1-13 (of LfcinB) form an alpha-helix. Hence, this region of lactoferricin B appears able to adopt a helical or sheetlike conformation, similar to what has been proposed for the amyloidogenic prion proteins and Alzheimer's beta-peptides. LfcinB has an extended hydrophobic surface comprised of residues Phe1, Cys3, Trp6, Trp8, Pro16, Ile18, and Cys20. The side chains of these residues are well-defined in the NMR structure. Many hydrophilic and positively charged residues surround the hydrophobic surface, giving LfcinB an amphipathic character. LfcinB bears numerous similarities to a vast number of cationic peptides which exert their antimicrobial activities through membrane 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 relevant to membrane interaction than that suggested by the X-ray structure of intact lactoferrin. Based on the solution structure, it is now possible to propose potential mechanisms for the antimicrobial action of LfcinB.

MH Amino Acid Sequence; Animal; Anti-Infective Agents/*chemistry; Antibiotics, Peptide/*chemistry; Cattle; Crystallography, X-Ray; Lactoferrin/*analogs & derivatives/chemistry; Models, Molecular; Molecular Sequence Data; Peptides/*chemistry; Protein Structure, Secondary; Protons; Solutions; Support, Non-U.S. Gov't

AD Department of Biological Sciences, University of Calgary, Alberta, Canada.

SP englisch

PO USA

EA pdf-Datei

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