The Involvement of Amino Acid Side Chains in Shielding the Nickel Coordination Site: An NMR Study

Abstract

Abstract:Coordination of proteins and peptides to metal ions is known to affect their properties, often by a change in their structural organization. Side chains of the residues directly involved in metal binding or very close to the coordination centre may arrange themselves around it, in such a way that they can, for instance, disrupt the protein functions or stabilize a metal complex by shielding it from the attack of water or other small molecules. The conformation of these side chains may be crucial to different biological or toxic processes. In our research we have encountered such behaviour in several cases, leading to interesting results for our purposes. Here we give an overview on the structural changes involving peptide side chains induced by Ni(II) coordination. In this paper we deal with a number of peptides, deriving from proteins containing one or more metal coordinating sites, which have been studied through a series of NMR experiments in their structural changes caused by Ni(II) complexation. Several peptides have been included in the study: short sequences from serum albumin (HSA), Des-Angiotensinogen, the 30-amino acid tail of histone H4, some fragments from histone H2A and H2B, the initial fragment of human protamine HP2 and selected fragments from prion and Cap43 proteins. NMR was the election technique for gathering structural information. Experiments performed for this purpose included 1D 1 H and 13 C, and 2D HSQC, COSY, TOCSY, NOESY and ROESY acquisitions, which allowed the calculation of the Ni(II) complexes structural models.

Analysis of nickel distribution by synchrotron radiation X-ray fluorescence in nickel-induced early- and late-phase allergic contact dermatitis in Hartley guinea pigs

“…Some reports found and proved this phenomenon of nickel metal-binding amino acids, peptides, or proteins in vitro . [22–24] Our study demonstrated nickel binding events for nickel contact allergy in vivo by the measurement of XANES. Some relative studies have reported that Ni 2+ triggered an inflammatory response by directly activating human Toll-like receptor 4 (TLR4) in vitro , and they demonstrated that Ni 2+ -induced ACD symptoms were species-specific, as the mouse TLR family could not generate this response; mouse TLR senses microbial pathogens and endogenous ligands.…”

Nuclear factor erythroid 2 – related factor 2 and its relationship with cellular response in nickel exposure: a systems biology analysis

“…In NiSO 4 and other soluble NCC, Ni 2+ can bond to soluble proteins on antigen-presenting cells (APC) [63]. APCs recognize this Ni 2+ -protein complex as an antigen, causing the activation of naïve T cells [64], which subsequently differentiate to Ni 2+ -specific interferon γ (IFN-γ)-producing CD4+ and CD8+ effector T cells [65], involved in Ni allergies. Ni 2+ also activates the expression of intercellular adhesion molecules on endothelial cells and keratinocytes, therefore amplifying the inflammatory response [66].…”

Metal complexes of amino acids and peptides

“…176 A series of the N-terminally modified derivatives of ATCUNmotif peptides have also been studied and it was found that the stability of their Cu(II) complexes is governed by the acidity of the N-terminal amino nitrogen in the peptides. 183 3.2 Metal complexes of biologically active peptides containing His residues Some 10-15 years ago the discovery of the possible role of metal ions in the various forms of neurodegenerative disorders (e.g. One of the histidines is present in internal position, while the others are related to the high affinity metal binding sites providing a good chance to compare the metal binding affinity of the His sites in different environments.…”