Crystal structures of human CaMKIalpha reveal insights into the regulation mechanism of CaMKI.
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Zha M, Zhong C, Ou Y, Han L, Wang J, Ding J
Crystal structures of human CaMKIalpha reveal insights into the regulation mechanism of CaMKI.
PLoS One. 2012;7(9):e44828. doi: 10.1371/journal.pone.0044828. Epub 2012 Sep 20.
- PubMed ID
- 23028635 [ View in PubMed]
- Abstract
Human calcium/calmodulin-dependent protein kinase I (CaMKI) plays pivotal roles in the nervous system. The activity of human CaMKI is regulated by a regulatory region including an autoinhibitory segment and a CaM-binding segment. We report here four structures of three CaMKIalpha truncates in apo form and in complexes with ATP. In an apo, autoinhibited structure, the activation segment adopts a unique helical conformation which together with the autoinhibitory segment constrains helices alphaC and alphaD in inactive conformations, sequesters Thr177 from being phosphorylated, and occludes the substrate-binding site. In an ATP-bound, inactive structure, the activation segment is largely disordered and the CaM-binding segment protrudes out ready for CaM binding. In an ATP-bound, active structure, the regulatory region is dissociated from the catalytic core and the catalytic site assumes an active conformation. Detailed structural analyses reveal the interplay of the regulatory region, the activation segment, and the nucleotide-binding site in the regulation of CaMKI.