Vol. 1, No. 3, 2009
Issue release date: April 2009
J Innate Immun 2009;1:268–280
(DOI:10.1159/000174822)
Research Article
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The Central Kink Region of Fowlicidin-2, an α-Helical Host Defense Peptide, Is Critically Involved in Bacterial Killing and Endotoxin Neutralization

Xiao Y.a · Herrera A.I.c · Bommineni Y.R.a · Soulages J.L.b · Prakash O.c · Zhang G.a
Departments of aAnimal Science and bBiochemistry and Molecular Biology, Oklahoma State University, Stillwater, Okla., and cDepartment of Biochemistry, Kansas State University, Manhattan, Kans., USA
email Corresponding Author


 goto top of outline Key Words

  • Host defense peptide
  • Antimicrobial peptides
  • Cathelicidins
  • Innate immunity
  • Structure-activity relationship
  • Endotoxin
  • Antibiotic resistance

 goto top of outline Abstract

Fowlicidins are a group of newly identified chicken cathelicidin host defense peptides. We have shown that the putatively mature fowlicidin-2 of 31 amino acid residues possesses potent antibacterial and lipopolysaccharide (LPS)- neutralizing activities, but with a noticeable toxicity to mammalian cells. As a first step in exploring the structure-activity relationships of fowlicidin-2, in this study we determined its tertiary structure by nuclear magnetic resonance spectroscopy. Unlike the majority of cathelicidins, which are composed of a predominant α-helix with a short hinge sequence near the center, fowlicidin-2 consists of 2 well-defined α-helical segments (residues 6–12 and 23–27) connected by a long extensive kink (residues 13–20) induced by proline. To further investigate the functional significance of each of these structural components, several N- and C-terminal deletion analogs of fowlicidin-2 were synthesized and analyzed for their antibacterial, cytotoxic and LPS-neutralizing activities. Our results indicated that neither the N- nor C-terminal α-helix alone is sufficient to confer any function. Rather, fowlicidin-2(1–18) and fowlicidin-2(15–31), 2 α-helical segments with inclusion of the central cationic kink region, retained substantial capacities to kill bacteria and neutralize the LPS-induced proinflammatory response, relative to the parent peptide. More desirably, these 2 peptide analogs showed substantially reduced toxicity to human erythrocytes and epithelial cells, indicative of improved potential as antibacterial and antisepsis agents. To our knowledge, fowlicidin-2 is the first α-helical cathelicidin, with the central kink region shown to be critically important in killing bacteria and neutralizing LPS.

Copyright © 2008 S. Karger AG, Basel


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 goto top of outline Author Contacts

Dr. Guolong Zhang
Department of Animal Science, Oklahoma State University
212D Animal Science Bldg
Stillwater, OK 74078 (USA)
Tel. +1 405 744 6619, Fax +1 405 744 7390, E-Mail zguolon@okstate.edu


 goto top of outline Article Information

Y.X. and A.H. contributed equally to this paper.

Received: July 17, 2008
Accepted after revision: September 29, 2008
Published online: November 14, 2008
Number of Print Pages : 13
Number of Figures : 7, Number of Tables : 2, Number of References : 35


 goto top of outline Publication Details

Journal of Innate Immunity

Vol. 1, No. 3, Year 2009 (Cover Date: April 2009)

Journal Editor: Herwald H. (Lund), Egesten A. (Lund)
ISSN: 1662-811X (Print), eISSN: 1662-8128 (Online)

For additional information: http://www.karger.com/JIN


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