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Oligomerization states of the association domain and the holoenyzme of Ca 2+ /CaM kinase II
Author(s) -
Rosenberg Oren S.,
Deindl Sebastian,
Comolli Luis R.,
Hoelz André,
Downing Kenneth H.,
Nairn Angus C.,
Kuriyan John
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.05088.x
Subject(s) - dodecameric protein , caenorhabditis elegans , crystallography , chemistry , electron micrographs , protein kinase a , protein kinase domain , kinase , domain (mathematical analysis) , proteolysis , biophysics , electron microscope , biology , biochemistry , enzyme , physics , dna , gene , mathematical analysis , mathematics , mutant , optics
Ca 2+ /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 ≈ 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 CaMKIIα 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 ≈ 1–335 residues and that the removal of this region allows the association domain to convert into a more stable 7‐fold symmetric form.