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|Title:||Metal ions modulate the folding and stability of the tumor suppressor protein S100A2|
|Authors:||Botelho, Hugo M.|
Gomes, Cláudio M.
protein structure and folding
|Citation:||Botelho, H. M., Koch, M., Fritz, G., and Gomes, C. M. (2009) Metal ions modulate the folding and stability of the tumor suppressor protein S100A2, Febs J 276, 1776-1786|
|Abstract:||The EF-hand protein S100A2 is a cell cycle regulator involved in tumorigenesis, acting through regulation of the p53 activation state. Metal ion-free S100A2 is homodimeric and contains two Ca2+-binding sites and two Zn2+-binding sites per subunit, whereby the Zn2+ ion binding to one of the sites is coordinated by residues from two homodimers. The effect of selective binding of these metal ions was investigated using site-specific mutants which lacked one or both zinc sites. CD analysis of secondary structure changes on metallation showed that Zn2+ binding was associated with a decrease in the secondary structure content, whereas Ca2+ had the opposite effect in two of the three S100A2 mutants studied. The energy of unfolding DeltaGU of the apo wild-type S100A2 was determined to be 89.9 kJ.mol-1, and the apparent midpoint transition temperature (Tmapp) was 58.4ºC. In addition, a detailed study of the urea and thermal unfolding of the S100A2 mutants in different metallation states (apo, Zn2+ and Ca2+) was performed. Thermal denaturation experiments showed that Zn2+ acts as a destabilizer and Ca2+ as a stabilizer of the protein conformation. This suggests a synergistic effect between metal binding, protein stability and S100A2 biological activity, according to which Ca2+ activates and stabilizes the protein, the opposite being observed on Zn2+ binding.|
|Description:||Febs Journal (2009)276:1776-1786|
|Appears in Collections:||ITQB: PBFS - Artigos em revista internacional com arbitragem científica|
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|2009 - Botelho - FEBS J.pdf||Main article||534,12 kB||Adobe PDF||View/Open|
|2009 - Botelho - FEBS J - supplementary.pdf||Supplementary information||53,17 kB||Adobe PDF||View/Open|
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