Probing S100A12 Interactions with Model Membranes

Proteins belonging to the S100 family regulate many cellular functions, including cell growth, differentiation, motility, contraction and intracellular signal transduction. S100A12 is a small calcium-binding protein highly abundant in the cytosol of granulocytes, where it has a possible role in signal modulation of inflammatory processes.In this study, the binding of porcine S100A12 (Calgranulin C) to lipid bilayers and the effect of ions (calcium and zinc) in modulating its interaction with liposomes was investigated using synchrotron radiation circular dichroism (SRCD), fluorescence emission and surface plasmon resonance spectroscopies.The binding of S100A12 to phospholipid vesicles occurred both in its apo- and holo- forms, however the protein was bound more tightly to negatively-charged liposomes. Moreover, the presence of the ions facilitated its interaction with liposomes, producing distinct conformational changes and severely reducing its thermal stability.These S100A12-lipid interactions may be a way of translating physiological changes in calcium/zinc levels into specific cellular responses. In addition S100A12 may exist in a dynamic exchange between cytosolic and membrane-associated states, regulated by specific cellular signals.(Support by grants from FAPESP, CNPq and the BBRSC, and beamtime from the ISA Synchrotron facility, Denmark).