The effect of deleting residue C269 in the β12-β13 loop of protein phosphatase 2A (PP2A)catalytic subunit on the interaction between PP2A and metal ions, especially Mn2+

Protein phosphatase 2A (PP2A) is one of the most important Ser/Thr phosphatases in eukaryotic cells. The enzymatic core of PP2A (PP2A(D)) consists of a scaffold subunit (A subunit) and a catalytic subunit (C subunit). When residue Cys269 in the beta 12-beta 13 loop of the PP2A C subunit was deleted (Delta C269), the activity and the intrinsic fluorescence intensity of PP2A(D) decreased. Specify the effects of some metal ions on PP2A(D) were also changed. Mn2+ in particular was an efficient activator of Delta C269 and altered the intrinsic fluorescence spectrum of Delta C269. Remarkably, after pre-treatment of Delta C269 with Mn2+, the effects of other metal ions showed the same trends as they had on the WT. Molecular dynamics (MD) simulations showed that deletion of Cys269 decreased the polarity of the beta 12-beta 13 loop of PP2A C alpha. We conclude that deletion of residue Cys269 alters the conformation and activity of PP2A(D) and influences the interaction between PP2A and various metal ions, notably Mn2+. (C) 2011 Elsevier B.V. All rights reserved.