| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2036129 | Cell | 2011 | 14 Pages |
SummaryCalcium/calmodulin-dependent kinase II (CaMKII) forms a highly conserved dodecameric assembly that is sensitive to the frequency of calcium pulse trains. Neither the structure of the dodecameric assembly nor how it regulates CaMKII are known. We present the crystal structure of an autoinhibited full-length human CaMKII holoenzyme, revealing an unexpected compact arrangement of kinase domains docked against a central hub, with the calmodulin-binding sites completely inaccessible. We show that this compact docking is important for the autoinhibition of the kinase domains and for setting the calcium response of the holoenzyme. Comparison of CaMKII isoforms, which differ in the length of the linker between the kinase domain and the hub, demonstrates that these interactions can be strengthened or weakened by changes in linker length. This equilibrium between autoinhibited states provides a simple mechanism for tuning the calcium response without changes in either the hub or the kinase domains.PaperFlick To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowHelp with MP4 filesOptionsDownload video (15284 K)
Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (277 K)Download as PowerPoint slideHighlights► Crystal structure of full-length human CaMKII holoenzyme ► The compact autoinhibited state is inaccessible to calmodulin binding ► Equilibrium between compact and open autoinhibited forms is controlled by a linker ► Altering linker length tunes the calcium threshold frequency for phosphorylation
