Human S100A3 tetramerization propagates Ca2Â +/Zn2Â + binding states

► We explored functional role of the C-terminal Zn2 +-binding domain unique to S100A3. ► Affinity to Ca2 + and Zn2 + of S100A3 was enhanced when the other cation bound. ► A single Zn2 + binding accelerates Ca2 +-dependent S100A3 tetramerization. ► Overall shape of an S100A3 tetramer is predicted by small angle scattering analyses. ► Cation binding states to each S100A3 subunit propagate within a homotetramer.