Structure of the Autoinhibited Kinase Domain of CaMKII and SAXS Analysis of the Holoenzyme
- 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:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1008665
- Journal Information:
- Cell, Vol. 123, Issue (5) ; 12, 2005; ISSN 0092-8674
- Country of Publication:
- United States
- Language:
- ENGLISH
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