Multilevel Changes in Protein Dynamics upon Complex Formation of the Calcium‐Loaded S100A4 with a Nonmuscle Myosin IIA Tail Fragment |
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| Authors: | Gyula Pálfy Bence Kiss László Nyitray Andrea Bodor |
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| Affiliation: | 1. Laboratory of Structural Chemistry and Biology, Institute of Chemistry, E?tv?s Loránd University, Budapest, Hungary;2. Department of Biochemistry, E?tv?s Loránd University, Budapest, Hungary |
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| Abstract: | Dysregulation of Ca2+‐binding S100 proteins plays important role in various diseases. The asymmetric complex of Ca2+‐bound S100A4 with nonmuscle myosin IIA 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. |
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| Keywords: | backbone dynamics Ca2+ affinity NMR spectroscopy protein– protein interactions S100A4 protein |
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