Three-dimensional reconstructions of calcium/calmodulin-dependent (CaM) kinase IIalpha and truncated CaM kinase IIalpha reveal a unique organization for its structural core and functional domains.
Studies of the structural organization of calcium/ calmodulin-dependent protein kinase IIalpha (CaM KIIalpha) and truncated CaM KIIalpha by three-dimensional electron microscopy and protein engineering show that the structures consist of 12 subunits that are organized in two stacked hexameric rings with 622 symmetry. The body of CaM KIIalpha is gear-shaped, consisting of six slanted flanges, and has six foot-like processes attached by narrow appendages to both ends of the flanges. Truncated CaM KIIalpha that lacks functional domains has a structure that is very similar to the body of CaM KIIalpha. Thus, the functional domains reside in the foot-like processes, and the association domain comprises the gear-shaped core. The ribbon diagram of the bilobate structure of CaM KI fits nicely in the envelope of the foot-like component and indicates that the crevice between the two lobes comprising the functional domains is near the middle portion of the foot. The clustering of the functional domains provides a favorable arrangement for the autophosphorylation reaction, and the unusual arrangement of the catalytic domain on extended tethers appears to be significant for the remarkable functional diversity of CaM KIIalpha in cellular regulation.
Kolodziej
S J
SJ
Department of Pathology and Laboratory Medicine, University of Texas Health Science Center, Houston, Texas 77030, USA.
Hudmon
A
A
Waxham
M N
MN
Stoops
J K
JK
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D002384:Catalysis; D018076:DNA, Complementary; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008854:Microscopy, Electron; D011487:Protein Conformation; D051381:Rats; D014961:X-Ray Diffraction
D018076:DNA, Complementary; D007527:Isoenzymes; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517675:Camk2a protein, rat