Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium
- 2 May 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 17 (5), 596-601
- https://doi.org/10.1038/nsmb.1795
Abstract
A family of calcium-dependent protein kinases (CDPK), containing a calcium-binding domain, is present in apicomplexan parasites, ciliates and plants, but not in animals. Now crystal structures of CDPKs from Toxoplasma gondii and Cryptosporidium parvum in their apo or calcium-bound states reveal the structural reorganization induced by calcium that results in activation. Calcium-dependent protein kinases (CDPKs) have pivotal roles in the calcium-signaling pathway in plants, ciliates and apicomplexan parasites and comprise a calmodulin-dependent kinase (CaMK)-like kinase domain regulated by a calcium-binding domain in the C terminus. To understand this intramolecular mechanism of activation, we solved the structures of the autoinhibited (apo) and activated (calcium-bound) conformations of CDPKs from the apicomplexan parasites Toxoplasma gondii and Cryptosporidium parvum. In the apo form, the C-terminal CDPK activation domain (CAD) resembles a calmodulin protein with an unexpected long helix in the N terminus that inhibits the kinase domain in the same manner as CaMKII. Calcium binding triggers the reorganization of the CAD into a highly intricate fold, leading to its relocation around the base of the kinase domain to a site remote from the substrate binding site. This large conformational change constitutes a distinct mechanism in calcium signal-transduction pathways.Keywords
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