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J Biol Chem, Vol. 275, Issue 19, 14354-14359, May 12, 2000

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*

Steven J. KolodziejDagger , Andy Hudmon§, M. Neal Waxham§, and James K. StoopsDagger ||

From the Departments of Dagger  Pathology and Laboratory Medicine and § Neurobiology and Anatomy, University of Texas Health Science Center, Houston, Texas 77030

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.


* This work was supported in part by United States Public Health Service Grants NS 26086 (to N. M. W. and J. K. S.). A portion of this study is part of the dissertation presented by A. H. to the University of Texas Graduate School of Biomedical Sciences at Houston in partial fulfillment of the Ph.D. degree.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by Training Grant NS 07373 from NINDS, National Institutes of Health. Current address: Dept. of Neurobiology, Stanford University, Stanford, CA 94305.

|| To whom correspondence should be addressed. Tel.: 713-500-5345; Fax: 713-500-0730; E-mail: James.K.Stoops@uth.tmc.edu.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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