at Google ScholarTitle data
Bauer, Finn ; Schweimer, Kristian ; Klüver, Enno ; Conejo-Garcia, Jose-Ramon ; Forssmann, Wolf-Georg ; Rösch, Paul ; Adermann, Knut ; Sticht, Heinrich:
Structure determination of human and murine β-defensins reveals structural conservation in the absence of significant sequence similarity.
In: Protein Science.
Vol. 10
(2001)
Issue 12
.
- pp. 2470-2479.
ISSN 1469-896X
DOI: https://doi.org/10.1110/ps.24401
Abstract in another language
Defensins are cationic and cysteine-rich peptides that play a crucial role in the host defense against microorganisms of many organisms by their capability to permeabilize bacterial membranes. The low sequence similarity among the members of the large mammalian β-defensin family suggests that their antimicrobial activity is largely independent of their primary structure. To investigate to what extent these defensins share a similar fold, the structures of the two human β-defensins, hBD-1 and hBD-2, as well as those of two novel murine defensins, termed mBD-7 and mBD-8, were determined by nuclear magnetic resonance spectroscopy. All four defensins investigated share a striking similarity on the level of secondary and tertiary structure including the lack of a distinct hydrophobic core, suggesting that the fold is mainly stabilized by the presence of three disulfide bonds. In addition to the overall shape of the molecules, the ratio of solvent-exposed polar and hydrophobic side chains is also very similar among the four defensins investigated. It is significant that β-defensins do not exhibit a common pattern of charged and hydrophobic residues on the protein surface and that the β-defensin-specific fold appears to accommodate a wide range of different amino acids at most sequence positions. In addition to the implications for the mode of biological defensin actions, these findings are of particular interest because β-defensins have been suggested as lead compounds for the development of novel peptide antibiotics for the therapy of infectious diseases.