| Autor: |
Rosenberg OS; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA., Deindl S, Sung RJ, Nairn AC, Kuriyan J |
| Jazyk: |
angličtina |
| Zdroj: |
Cell [Cell] 2005 Dec 02; Vol. 123 (5), pp. 849-60. |
| DOI: |
10.1016/j.cell.2005.10.029 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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