CK2 is a protein kinase essential for cell viability whose activity is altered in several cancers. Its mechanisms of regulation differ from those common to other eukaryotic protein kinases and are not entirely established yet. Here we present crystal structures of the monomeric form of the alpha(2)beta(2) holoenzyme that allow refining a formerly proposed structural model for activity regulation by oligomerization. Previous crystal structures of the CK2 holoenzyme show an asymmetric arrangement of the two alpha catalytic subunits around the obligate beta(2) regulatory subunits. Asymmetric alpha(2)beta(2) tetramers are organized in trimeric rings that correspond to inactive forms of the enzyme. The new crystal structures presented here reveal the symmetric architecture of the isolated active tetramers. The dimension and the nature of the alpha/beta interfaces configure the holoenzyme as a strong complex that does not spontaneously dissociate in solution, in accordance with the low dissociation constant (similar to 4 nM).

Active Form of the Protein Kinase CK2 alpha(2)beta(2) holoenzyme Is a Strong Complex with Symmetric Architecture

LOLLI, GRAZIANO;RANCHIO, ALESSANDRO;BATTISTUTTA, ROBERTO
2014

Abstract

CK2 is a protein kinase essential for cell viability whose activity is altered in several cancers. Its mechanisms of regulation differ from those common to other eukaryotic protein kinases and are not entirely established yet. Here we present crystal structures of the monomeric form of the alpha(2)beta(2) holoenzyme that allow refining a formerly proposed structural model for activity regulation by oligomerization. Previous crystal structures of the CK2 holoenzyme show an asymmetric arrangement of the two alpha catalytic subunits around the obligate beta(2) regulatory subunits. Asymmetric alpha(2)beta(2) tetramers are organized in trimeric rings that correspond to inactive forms of the enzyme. The new crystal structures presented here reveal the symmetric architecture of the isolated active tetramers. The dimension and the nature of the alpha/beta interfaces configure the holoenzyme as a strong complex that does not spontaneously dissociate in solution, in accordance with the low dissociation constant (similar to 4 nM).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3133725
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