title: Multilevel Changes in Protein Dynamics upon Complex Formation of the Calcium-Loaded S100A4 with a Nonmuscle Myosin IIA Tail Fragment.
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.
authors.affiliation: Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány Péter sétány 1 A, 1117, Budapest, Hungary.
authors.forename: Gyula
authors.initials: G
authors.lastname: Pálfy
authors.affiliation: Department of Biochemistry, Eötvös Loránd University, Pázmány Péter sétány 1/C, 1117, Budapest, Hungary.
authors.forename: Bence
authors.initials: B
authors.lastname: Kiss
authors.affiliation: Department of Biochemistry, Eötvös Loránd University, Pázmány Péter sétány 1/C, 1117, Budapest, Hungary. nyitray@elte.hu.
authors.forename: László
authors.initials: L
authors.lastname: Nyitray
authors.affiliation: Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány Péter sétány 1 A, 1117, Budapest, Hungary. abodor@chem.elte.hu.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bodor
mesh_terms: D002118:Calcium / Q000378:metabolism*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D024507:Nonmuscle Myosin Type IIA / Q000737:chemistry* / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D000071999:S100 Calcium-Binding Protein A4 / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000071999:S100 Calcium-Binding Protein A4; D024507:Nonmuscle Myosin Type IIA; D002118:Calcium
keywords: Ca2+ affinity; NMR spectroscopy; S100A4 protein; backbone dynamics; protein-protein interactions