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

Rosenberg OS, Deindl S, Sung RJ, Nairn AC, Kuriyan J

Cell 123 (5) 849-860 [2005-12-02; online 2005-12-06]

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.

Sebastian Deindl

QC bibliography QC xrefs

PubMed 16325579

DOI 10.1016/j.cell.2005.10.029

Crossref 10.1016/j.cell.2005.10.029

pii: S0092-8674(05)01173-6