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Post-translational S-Nitrosylation Is an Endogenous Factor Fine Tuning the Properties of Human S100A1 Protein

Lenarčič Živković, Martina and Zaręba-Kozioł, Monika and Zhukova, Liliya and Poznański, Jarosław and Zhukov, Igor and Wysłouch-Cieszyńska, Aleksandra (2012) Post-translational S-Nitrosylation Is an Endogenous Factor Fine Tuning the Properties of Human S100A1 Protein. The Journal of biological chemistry, 287 (48). pp. 40457-40470. ISSN 1083-351X

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Official URL: http://www.jbc.org/content/287/48/40457.full


S100A1 is a member of the Ca2+-binding S100 protein family. It is expressed in brain and heart tissue, where it plays a crucial role as a modulator of Ca2+ 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 Cys85 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 Ca2+-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 Cys85 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 Ca2+ signal transmitter sensitive to NO/redox equilibrium within cells.

Item Type:Article
Subjects:Q Science > QC Physics
Q Science > QD Chemistry
Divisions:Department of Biophysics
ID Code:526
Deposited By: doctor Monika Zaręba-Kozioł
Deposited On:03 Apr 2013 10:43
Last Modified:15 Oct 2014 10:34

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