Structure of the autoinhibited kinase domain of CaMKII and SAXS analysis of the holoenzyme - PubMed (original) (raw)

. 2005 Dec 2;123(5):849-60.

doi: 10.1016/j.cell.2005.10.029.

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

Oren S Rosenberg et al. Cell. 2005.

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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.

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