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

Dysregulation of Ca(2+) -binding S100 proteins plays important role in various diseases. The asymmetric complex of Ca(2+) -bound S100A4 with nonmuscle myosin IIA has high stability and highly increased Ca(2+) 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 Ca(2+) -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 Ca(2+) affinity. These multilevel changes in protein dynamics as conformational adaptation allow S100A4 fine-tuning of its protein-protein interactions inside the cell during Ca(2+) signaling.