Multilevel Changes in Protein Dynamics upon Complex Formation of the Calcium-Loaded S100A4 with a Nonmuscle Myosin IIA Tail Fragment

Dysregulation of Ca2+-binding S100 proteins plays important role in various diseases. The asymmetric complex of Ca2+-bound S100A4 with nonmuscle myosinIIA has high stability and highly increased Ca2+ affinity. Here we investigated the possible causes of this allosteric effect by NMR spectroscopy. Chemical shift-based secondary-structure analysis did not show substantial changes for the complex. Backbone dynamics revealed slow-timescale local motions in the H1 helices of homodimeric S100A4; these were less pronounced in the complex form and might be accompanied by an increase in dimer stability. Different mobilities in the Ca2+-coordinating EF-hand sites indicate that they communicate by an allosteric mechanism operating through changes in protein dynamics; this must be responsible for the elevated Ca2+ affinity. These multilevel changes in protein dynamics as conformational adaptation allow S100A4 fine-tuning of its protein-protein interactions inside the cell during Ca2+ signaling.