Dimerization of Peptides by Calcium Ions: Investigation of a Calcium-Binding Motif

We investigated calcium-binding motifs of peptides and their recognition of active functionalities for coordination. This investigation generates the fundamentals to design carrier material for calcium-bound peptide-peptide interactions. Interactions of different peptides with active calcium domains were investigated. Evaluation of selectivity was performed by electrospray ionization mass spectrometry by infusing solutions containing two different peptides (P1 and P2) in the presence of calcium ions. In addition to signals for monomer species, intense dimer signals are observed for the heterodimer ions ( represents the noncovalent binding of calcium with the peptide) in the positive ion mode and for ions in the negative ion mode. Monitoring of the dissociation from these mass selected dimer ions via the kinetic method provides information on the calcium affinity order of different peptide sequences. The authors fondly remember the late Mario Ursem as a passionate person and friend interested in research and in the researchers themselves. In particular, the exploration and discovery of new chromatography materials was one of his great achievements 1. Introduction Calcium is one of the most abundant cations in living organisms [1, 2]. As an intracellular signaling ion, Ca2+ plays crucial roles in an array of cellular functions from fertilization, muscle contraction, and cell differentiation/proliferation to apoptosis and, in the case of dysregulation, cancer and neural diseases [3–6]. The impact of monitoring calcium in proteins can be extremely high. For example, mutations in calcium ion transport proteins can disrupt channel functions and have been associated with various diseases, like Alzheimer’s disease [6]. However, Ca2+ does not act alone. Many cells contain a variety of cytosolic calcium-binding proteins (CaBPs) which either modulate or mediate the actions of this ion [7–9]. Depending on the role and cellular locations of the CaBPs, their affinities may vary by as much as 106-fold [10]. These proteins may be found just in specific cell types or are distributed in variety of cells and tissues. For instance, Table 1 summarizes major calcium-binding proteins present in the nervous system [7]. Table 1: Major calcium-binding proteins in the nervous system. Three major classes of Ca2+-sensing structural modules have been identified as EF-hands [11], C2 domains, and annexin folds [12]. The EF-hand domain is one of the common known motifs to bind calcium to proteins [13, 14]. Falke et al. [15] and Linse and Forsén [16] have shown the finely tuned