With all other S100 proteins S100A12 shares key structural motifs. The protein can bind different bivalent ions, preferentially Ca2+ and Zn2+. Ion-binding can be of intracellular functional relevance for S100A12; an involvement in buffering intra- versus extracellular Zn2+ in cross-talk with Ca2+ has been proposed . In addition metal-ion binding by S100A12 has pronounced impact on protein conformation and consequently oligomerization. One focus of our research is on the evaluation of differential extracellular functions of S100A12 oligomers.
This is performed by the introduction of site directed mutations (SDM) into the S100A12 sequence. These result in an exchange of amino acids contributing to Ca2+ or Zn2+-binding against Alanine. Corresponding S100A12-mutants are expressed both in E. coli as well as a mammalian expression system. The overall aim is to generate S100A12-complexes with defined size, which can be analyzed for receptor binding and signalling. Thus, pro-inflammatory complex forms of S100A12 shall be identified.