Crystal structure of the Ca 2+ ‐form and Ca 2+ ‐binding kinetics of metastasis‐associated protein, S100A4

S100A4 takes part in control of tumour cell migration and contributes to metastatic spread in in vivo models. In the active dimeric Ca 2+ ‐bound state it interacts with multiple intracellular targets. Conversely, oligomeric forms of S100A4 are linked with the extracellular function of this protein. We report the 1.5 Å X‐ray crystal structure of Ca 2+ ‐bound S100A4 and use it to identify the residues involved in target recognition and to derive a model of the oligomeric state. We applied stopped‐flow analysis of tyrosine fluorescence to derive kinetics of S100A4 activation by Ca 2+ ( k on = 3.5 μM −1 s −1 , k off = 20 s −1 ).