title: Oligomerization states of the association domain and the holoenyzme of Ca2+/CaM kinase II.
abstract: Ca2+/calmodulin activated protein kinase II (CaMKII) is an oligomeric protein kinase with a unique holoenyzme architecture. The subunits of CaMKII are bound together into the holoenzyme by the association domain, a C-terminal region of approximately 140 residues in the CaMKII polypeptide. Single particle analyses of electron micrographs have suggested previously that the holoenyzme forms a dodecamer that contains two stacked 6-fold symmetric rings. In contrast, a recent crystal structure of the isolated association domain of mouse CaMKIIalpha has revealed a tetradecameric assembly with two stacked 7-fold symmetric rings. In this study, we have determined the crystal structure of the Caenorhabditis elegans CaMKII association domain and it too forms a tetradecamer. We also show by electron microscopy that in its fully assembled form the CaMKII holoenzyme is a dodecamer but without the kinase domains, either from expression of the isolated association domain in bacteria or following their removal by proteolysis, the association domains form a tetradecamer. We speculate that the holoenzyme is held in its 6-fold symmetric state by the interactions of the N-terminal approximately 1-335 residues and that the removal of this region allows the association domain to convert into a more stable 7-fold symmetric form.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202, USA.
authors.forename: Oren S
authors.initials: OS
authors.lastname: Rosenberg
authors.forename: Sebastian
authors.initials: S
authors.lastname: Deindl
authors.forename: Luis R
authors.initials: LR
authors.lastname: Comolli
authors.forename: André
authors.initials: A
authors.lastname: Hoelz
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Downing
authors.forename: Angus C
authors.initials: AC
authors.lastname: Nairn
authors.forename: John
authors.initials: J
authors.lastname: Kuriyan
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D020035:Holoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D007527:Isoenzymes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D020035:Holoenzymes; D007527:Isoenzymes; D021122:Protein Subunits; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517679:unc-43 protein, C elegans