The coordination properties of a small peptide fragment from Human TLR4 sequence are relevant in Nickel Allergy mechanism

Nickel Allergy (NA) is a contact allergy which could occur in sensitised persons exposed for long periods of time to objects containing Nickel. In recent years, the human TLR4 (hTLR4) has been recognized as a key target in the Nickel-induced inflammation that eventually lead to allergy symptoms [1]. A peptide of 32 amino acids from 429-460 sequence of hTLR4 receptor has been selected as a simplified model to study the molecular mechanism of NA. The fragment contains three histidines, the non-conserved H431, and the conserved H456 and H458 in human (Fig. 1) which could be important for Ni(II) activation hTLR4 and to trigger an inflammatory response. The aim of our study was to confirm the coordination ability of a peptide fragment toward the H456 and H458 histidines potentially involved in hTLR4 activation. Spectroscopic (NMR, UV-Vis, CD, MS) and potentiometric techniques confirm the important role of the histidine-rich 429- 460 hTLR4 fragment in Ni(II) coordination and its relevance in NA mechanism [2].