Interaction of Human β-Defensin 2 (HBD2) with Glycosaminoglycans

Abstract

Human -defensin 2 (HBD2) is a member of the defensin family of antimicrobial peptides that plays important roles in the innate and adaptive immune system of both vertebrates and invertebrates. In addition to their direct bactericidal action, defensins are also involved in chemotaxis and Toll-like receptor activation. In analogy to chemokine/glycosaminoglycan (GAG) interactions, GAG-defensin complexes are likely to play an important role in chemotaxis and in presenting defensins to their receptors. Using a gel mobility shift assay, we found that HBD2 bound to a range of GAGs including heparin/heparan sulfate (HS), dermatan sulfate (DS) and chondroitin sulfate. We used NMR nESI, nano-electrospray ionization.

High molecular weight hyaluronic acid: a two‐pronged protectant against infection of the urogenital tract?

“…BD2 peptide molecules are positively charged and have been reported to bind to negatively charged GAGs 51. It is therefore possible that precipitation of the BD2‐GAG complexes on the epithelial cell surface masked the in vitro increase in BD2 concentrations in response to flagellin.…”

Pharmacology of Heparin and Related Drugs

“…Heparin binding site mapped; heparin pentasaccharide induced dimerization (unlike DS hexasaccharide) (Seo et al, 2010) NMR titration and high pressure NMR "Sandwich-like" dimerization mode proposed (De Paula et al, 2014) Cytotoxic mediators ECP NMR spectroscopy and crystal structure (2LVZ.pdb) with synthetic trisaccharide…”

Unique Properties of Human β-Defensin 6 (hBD6) and Glycosaminoglycan Complex

“…There are only two studies of GAG recognition by ␤-defensins: hBD6, in this work, and hBD2 (22). There is a limited sequence homology among the human ␤-defensins.…”

“…1B). Interestingly, both hBD2 and chemokines can interact with a heparin mimetic with similar micromolar affinities (22,32). Fig.…”

“…The binding sites for GAGs on hBD2 and the dimeric state of the hBD2-GAG complex were described recently using NMR spectroscopy and mass spectrometry (22). To further examine this interaction, we chose to study hBD6, a monomeric defensin that is constitutively expressed in epithelial cells from the epididymis, testis, and lung (23) and known to bind to the N-terminal sulfopeptide of the CCR2 receptor (24).…”