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From Proteopedia
Structure of a human CK2alpha prime, the paralog isoform of the catalytic subunit of protein kinase CK2 from Homo sapiens
Structural highlights
FunctionCSK22_HUMAN Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV.[1] [2] [3] Publication Abstract from PubMedProtein kinase CK2 (formerly "casein kinase 2") is composed of a central dimer of noncatalytic subunits (CK2beta) binding two catalytic subunits. In humans, there are two isoforms of the catalytic subunit (and an additional splicing variant), one of which (CK2alpha) is well characterized. To supplement the limited biochemical knowledge about the second paralog (CK2alpha'), we developed a well-soluble catalytically active full-length mutant of human CK2alpha', characterized it by Michaelis-Menten kinetics and isothermal titration calorimetry, and determined its crystal structure to a resolution of 2 A. The affinity of CK2alpha' for CK2beta is about 12 times lower than that of CK2alpha and is less driven by enthalpy. This result fits the observation that the beta4/beta5 loop, a key element of the CK2alpha/CK2beta interface, adopts an open conformation in CK2alpha', while in CK2alpha, it opens only after assembly with CK2beta. The open beta4/beta5 loop in CK2alpha' is stabilized by two elements that are absent in CK2alpha: (1) the extension of the N-terminal beta-sheet by an additional beta-strand, and (2) the filling of a conserved hydrophobic cavity between the beta4/beta5 loop and helix alphaC by a tryptophan residue. Moreover, the interdomain hinge region of CK2alpha' adopts a fully functional conformation, while unbound CK2alpha is often found with a nonproductive hinge conformation that is overcome only by CK2beta binding. Taken together, CK2alpha' exhibits a significantly lower affinity for CK2beta than CK2alpha; moreover, in functionally critical regions, it is less dependent on CK2beta to obtain a fully functional conformation. Structure of the Human Protein Kinase CK2 Catalytic Subunit CK2alpha' and Interaction Thermodynamics with the Regulatory Subunit CK2beta.,Bischoff N, Olsen B, Raaf J, Bretner M, Issinger OG, Niefind K J Mol Biol. 2011 Mar 18;407(1):1-12. Epub 2011 Jan 15. PMID:21241709[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Bischoff N | Bretner M | Issinger O-G | Niefind K | Olsen B | Raaf J
