The regulatory β subunit of protein kinase CK2 contributes to the recognition of the substrate consensus sequence. A study with an eIF2β-derived peptide

Giorgia Poletto, Jordi Vilardell, Oriano Marin, Mario A. Pagano, Giorgio Cozza, Stefania Sarno, Antoni Falqués, Emilio Itarte, Lorenzo A. Pinna, Flavio Meggio

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Resum

CK2 is a ubiquitous and pleiotropic Ser/Thr-specific protein kinase that phosphorylates more than 300 protein substrates at sites specified by an acidic consensus sequence in which positions n + 3 and n + 1 are particularly important. Recognition of substrates by CK2 is known to rely on basic residues located in the catalytic site of the α subunit which make electrostatic contacts with the negative charges in the substrate consensus sequence, thereby assuring optimal binding; the regulatory β subunit is believed to play a protective and stabilizing role. We describe a biochemical and structural analysis of CK2-mediated phosphorylation of a 22-mer synthetic peptide corresponding to the N-terminal tail of the eukaryotic translation initiation factor eIF2β. Results demonstrate that this peptide still displays phosphorylation features similar to full-length eIF2β and the CK2 β subunit also contributes to recognition of the protein substrate by establishing both polar and hydrophobic interactions with specificity determinants located downstream from the phosphoacceptor site. In particular, the N-terminal domain of the β subunit appears to be of crucial importance for optimizing high-affinity phosphorylation of the eIF2β peptide. This domain includes an acidic cluster whose electrostatic contacts with basic residues of the substrate attenuate intrasteric pseudosubstrate inhibition while strengthening substrate-kinase binding. © 2008 American Chemical Society.
Idioma originalEnglish
Pàgines (de-a)8317-8325
RevistaBiochemistry
Volum47
Número32
DOIs
Estat de la publicacióPublicada - 12 d’ag. 2008

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