2llt

Post-translational S-nitrosylation is an endogenous factor fine-tuning human S100A1 protein properties

spinqualitylabelsall models 2llt Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2llt is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SNC Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function S10A1_HUMAN Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Publication Abstract from PubMed S100A1 is a member of the Ca(2+)-binding S100 protein family. It is expressed in brain and heart tissue, where it plays a crucial role as a modulator of Ca(2+) homeostasis, energy metabolism, neurotransmitter release, and contractile performance. Biological effects of S100A1 have been attributed to its direct interaction with a variety of target proteins. The (patho)physiological relevance of S100A1 makes it an important molecular target for future therapeutic intervention. S-Nitrosylation is a post-translational modification of proteins, which plays a role in cellular signal transduction under physiological and pathological conditions. In this study, we confirmed that S100A1 protein is endogenously modified by Cys(85) S-nitrosylation in PC12 cells, which are a well established model system for studying S100A1 function. We used isothermal calorimetry to show that S-nitrosylation facilitates the formation of Ca(2+)-loaded S100A1 at physiological ionic strength conditions. To establish the unique influence of the S-nitroso group, our study describes high resolution three-dimensional structures of human apo-S100A1 protein with the Cys(85) thiol group in reduced and S-nitrosylated states. Solution structures of the proteins are based on NMR data obtained at physiological ionic strength. Comparative analysis shows that S-nitrosylation fine tunes the overall architecture of S100A1 protein. Although the typical S100 protein intersubunit four-helix bundle is conserved upon S-nitrosylation, the conformation of S100A1 protein is reorganized at the sites most important for target recognition (i.e. the C-terminal helix and the linker connecting two EF-hand domains). In summary, this study discloses cysteine S-nitrosylation as a new factor responsible for increasing functional diversity of S100A1 and helps explain the role of S100A1 as a Ca(2+) signal transmitter sensitive to NO/redox equilibrium within cells. Post-translational S-Nitrosylation Is an Endogenous Factor Fine Tuning the Properties of Human S100A1 Protein.,Lenarcic Zivkovic M, Zareba-Koziol M, Zhukova L, Poznanski J, Zhukov I, Wyslouch-Cieszynska A J Biol Chem. 2012 Nov 23;287(48):40457-70. doi: 10.1074/jbc.M112.418392. Epub, 2012 Sep 18. PMID:22989881 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also S100 proteins 3D structures

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