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Metal ions modulate the folding and stability of the tumor suppressor protein S100A2

2009-03-10Artigo científico Acesso restrito
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dc.contributor.authorBotelho, Hugo M.
dc.contributor.authorKoch, Michael
dc.contributor.authorFritz, Günter
dc.contributor.authorGomes, Cláudio M.
dc.date.accessioned2011-04-05T15:22:22Z
dc.date.available2011-04-05T15:22:22Z
dc.date.issued2009-03-10
dc.descriptionFebs Journal (2009)276:1776-1786
dc.description.abstractThe 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.en_US
dc.identifier.citationBotelho, 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, 1776-1786en_US
dc.identifier.urihttp://hdl.handle.net/10362/5452
dc.language.isoengen_US
dc.publisherWileyen_US
dc.subjectcanceren_US
dc.subjectmetalsen_US
dc.subjectp53en_US
dc.subjectprotein stabilityen_US
dc.subjectprotein structure and foldingen_US
dc.titleMetal ions modulate the folding and stability of the tumor suppressor protein S100A2en_US
dc.typejournal article
dspace.entity.typePublication
my.embargo.termsnullen_US
rcaap.rightsclosedAccessen_US
rcaap.typearticleen_US

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