title: Mass Spectrometry Reveals Protein Kinase CK2 High-Order Oligomerization via the Circular and Linear Assembly.
abstract: CK2 is an intrinsically active protein kinase that is crucial for cellular viability. However, conventional kinase regulatory mechanisms do not apply to CK2, and its mode of regulation remains elusive. Interestingly, CK2 is known to undergo reversible ionic-strength-dependent oligomerization. Furthermore, a regulatory mechanism based on autoinhibitory oligomerization has been postulated on the basis of the observation of circular trimeric oligomers and linear CK2 assemblies in various crystal structures. Here, we employ native mass spectrometry to monitor the assembly of oligomeric CK2 species in an ionic-strength-dependent manner. A subsequent combination of ion mobility spectrometry-mass spectrometry and hydrogen-deuterium exchange mass spectrometry techniques was used to analyze the conformation of CK2 oligomers. Our findings support ionic-strength-dependent CK2 oligomerization, demonstrate the transient nature of the α/β interaction, and show that CK2 oligomerization proceeds via both the circular and linear assembly.
authors.affiliation: Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge, CB2 1EW, United Kingdom.
authors.forename: Wei-Guang
authors.initials: WG
authors.lastname: Seetoh
authors.affiliation: Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge, CB2 1EW, United Kingdom.
authors.forename: Daniel Shiu-Hin
authors.initials: DS
authors.lastname: Chan
authors.affiliation: Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge, CB2 1EW, United Kingdom.
authors.forename: Dijana
authors.initials: D
authors.lastname: Matak-Vinković
authors.affiliation: Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge, CB2 1EW, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Abell
mesh_terms: D000085:Acetates / Q000737:chemistry; D047390:Casein Kinase II / Q000737:chemistry; D003903:Deuterium; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D009994:Osmolar Concentration; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary
chemical_list: D000085:Acetates; D003903:Deuterium; C570325:CSNK2A1 protein, human; D047390:Casein Kinase II; C018824:ammonium acetate