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Nat Struct Mol Biol. 2010 May;17(5):596-601. doi: 10.1038/nsmb.1795. Epub 2010 May 2.

Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium.

Author information

1
Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.

Abstract

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.

PMID:
20436473
PMCID:
PMC3675764
DOI:
10.1038/nsmb.1795
[Indexed for MEDLINE]
Free PMC Article

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