Structure of the autoinhibited kinase domain of CaMKII and SAXS analysis of the holoenzyme

Oren S Rosenberg; Sebastian Deindl; Rou-Jia Sung; Angus C Nairn; John Kuriyan

doi:10.1016/j.cell.2005.10.029

Structure of the autoinhibited kinase domain of CaMKII and SAXS analysis of the holoenzyme

Cell. 2005 Dec 2;123(5):849-60. doi: 10.1016/j.cell.2005.10.029.

Authors

Oren S Rosenberg¹, Sebastian Deindl, Rou-Jia Sung, Angus C Nairn, John Kuriyan

Affiliation

¹ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

PMID: 16325579
DOI: 10.1016/j.cell.2005.10.029

Abstract

Ca2+/calmodulin-dependent protein kinase-II (CaMKII) is unique among protein kinases for its dodecameric assembly and its complex response to Ca2+. The crystal structure of the autoinhibited kinase domain of CaMKII, determined at 1.8 A resolution, reveals an unexpected dimeric organization in which the calmodulin-responsive regulatory segments form a coiled-coil strut that blocks peptide and ATP binding to the otherwise intrinsically active kinase domains. A threonine residue in the regulatory segment, which when phosphorylated renders CaMKII calmodulin independent, is held apart from the catalytic sites by the organization of the dimer. This ensures a strict Ca2+ dependence for initial activation. The structure of the kinase dimer, when combined with small-angle X-ray scattering data for the holoenzyme, suggests that inactive CaMKII forms tightly packed autoinhibited assemblies that convert upon activation into clusters of loosely tethered and independent kinase domains.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Binding Sites
Caenorhabditis elegans / enzymology
Caenorhabditis elegans Proteins / chemistry
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Calcium / metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases / chemistry*
Calcium-Calmodulin-Dependent Protein Kinases / genetics
Calcium-Calmodulin-Dependent Protein Kinases / metabolism
Calmodulin / metabolism
Crystallography, X-Ray
Dimerization
Holoenzymes / chemistry*
Holoenzymes / genetics
Holoenzymes / metabolism
Models, Molecular*
Molecular Sequence Data
Protein Structure, Quaternary
Protein Structure, Secondary
Protein Structure, Tertiary*
Sequence Alignment

Substances

Caenorhabditis elegans Proteins
Calmodulin
Holoenzymes
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
unc-43 protein, C elegans
Calcium