Universität zu Köln

Schnitzler, Alexander, Olsen, Birgitte Brinkmann, Issinger, Olaf-Georg and Niefind, Karsten ORCID: 0000-0002-0183-6315 (2014). The Protein Kinase CK2(Andante) Holoenzyme Structure Supports Proposed Models of Autoregulation and Trans-Autophosphorylation. J. Mol. Biol., 426 (9). S. 1871 - 1883. LONDON: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. ISSN 1089-8638

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Abstract

Eukaryotic protein kinases are typically strictly controlled by second messenger binding, protein/protein interactions, dephosphorylations or similar processes. None of these regulatory mechanisms is known to work for protein kinase CK2 (former name casein kinase 2), an acidophilic and constitutively active eukaryotic protein kinase. CK2 predbminantly exists as a heterotetrameric holoenzyme composed of two catalytic subunits (CK2 alpha) complexed to a dirner of non-catalytic subunits (CK2 beta). One model of CK2 regulation was proposed several times independently by theoretical docking of the first CK2 holoenzyme structure. According to this model, the CK2 holoenzyme forms autoinhibitory aggregates correlated with trans-autophosphorylation and driven by the down-regulatory affinity between an acidic loop of CK2 beta and the positively charged substrate binding region of CK2 alpha from a neighboring CK2 heterotetramer. Circular trimeric aggregates in which one-half of the CK2 alpha chains show the predicted inhibitory proximity between those regions were detected within the crystal packing of the human CK2 holoenzyme. Here, we present further in vitro support of the regulation-by-aggregationmodel by an alternative crystal form in which CK2 tetramers are arranged as approximately linear aggregates coinciding essentially with the early predictions. In this assembly, the substrate binding region of every CK2 alpha chain is blocked by a CK2 beta acidic loop from a neighboring tetramer. We found these crystals with CK2(Andante) that contains a CK2 beta variant mutated in a CK2 alpha-contact helix and described to be responsible for a prolonged circadian rhythm in Drosophila. The increased propensity of CK2(Andante) to form aggregates with completely blocked active sites may contribute to this phenotype. (c) 2014 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schnitzler, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Olsen, Birgitte Brinkmann UNSPECIFIED UNSPECIFIED UNSPECIFIED Issinger, Olaf-Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Niefind, Karsten UNSPECIFIED orcid.org/0000-0002-0183-6315 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-439368
DOI:	10.1016/j.jmb.2014.02.018
Journal or Publication Title:	J. Mol. Biol.
Volume:	426
Number:	9
Page Range:	S. 1871 - 1883
Date:	2014
Publisher:	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Place of Publication:	LONDON
ISSN:	1089-8638
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CRYSTAL-STRUCTURE; CASEIN KINASE-2; REGULATORY SUBUNIT; ENZYMATIC-ACTIVITY; CATALYTIC SUBUNIT; HUMAN CK2-ALPHA; BETA-SUBUNIT; CK2; PHOSPHORYLATION; INHIBITORS Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/43936