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

Amy K. Wernimont, Jennifer D. Artz, Patrick Finerty, Yu Hui Lin, Mehrnaz Amani, Abdellah Allali-Hassani, Guillermo Senisterra, Masoud Vedadi, Wolfram Tempel, Farrell MacKenzie, Irene Chau, Sebastian Lourido, L. David Sibley, Raymond Hui

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134 Scopus citations

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.

Original languageEnglish
Pages (from-to)596-601
Number of pages6
JournalNature Structural and Molecular Biology
Volume17
Issue number5
DOIs
StatePublished - May 1 2010

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    Wernimont, A. K., Artz, J. D., Finerty, P., Lin, Y. H., Amani, M., Allali-Hassani, A., Senisterra, G., Vedadi, M., Tempel, W., MacKenzie, F., Chau, I., Lourido, S., Sibley, L. D., & Hui, R. (2010). Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium. Nature Structural and Molecular Biology, 17(5), 596-601. https://doi.org/10.1038/nsmb.1795