Structure of the Autoinhibited Kinase Domain of CaMKII and SAXS Analysis of the Holoenzyme

Journal Article · Tue Jul 20 04:00:00 EDT 2010 · Cell

DOI:https://doi.org/10.1016/j.cell.2005.10.029· OSTI ID:1008665

Rosenberg, Oren S; Deindl, Sebastian; Sung, Rou-Jia; Nairn, Angus C; Kuriyan, John ^[1]

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1. Yale

Ca{sup 2+}/calmodulin-dependent protein kinase-II (CaMKII) is unique among protein kinases for its dodecameric assembly and its complex response to Ca{sup 2+}. The crystal structure of the autoinhibited kinase domain of CaMKII, determined at 1.8 {angstrom} 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 Ca{sup 2+} 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.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1008665
• Journal Information: Cell, Journal Name: Cell Journal Issue: (5) ; 12, 2005 Vol. 123; ISSN 0092-8674; ISSN CELLB5
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CALMODULIN
CRYSTAL STRUCTURE
PEPTIDES
PHOSPHOTRANSFERASES
PROTEINS
RESIDUES
RESOLUTION
SCATTERING
THREONINE