Three-dimensional solution structure of lactoferricin B, an antimicrobial peptide derived from bovine lactoferrin.
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.
Hwang
P M
PM
Department of Biological Sciences, University of Calgary, Alberta, Canada.
Zhou
N
N
Shan
X
X
Arrowsmith
C H
CH
Vogel
H J
HJ
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000737:chemistry*; D002417:Cattle; D018360:Crystallography, X-Ray; D007781:Lactoferrin / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011522:Protons; D012996:Solutions
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D010455:Peptides; D011522:Protons; D012996:Solutions; C082171:lactoferricin B; D007781:Lactoferrin