@article{8e271626180b4e2197b93bb48677b09f,
title = "Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium",
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.",
author = "Wernimont, {Amy K.} and Artz, {Jennifer D.} and Patrick Finerty and Lin, {Yu Hui} and Mehrnaz Amani and Abdellah Allali-Hassani and Guillermo Senisterra and Masoud Vedadi and Wolfram Tempel and Farrell MacKenzie and Irene Chau and Sebastian Lourido and Sibley, {L. David} and Raymond Hui",
note = "Funding Information: We thank J. Christodoulou, O. Billker, S. Knapp, T. Heightman, M. Schapira, C. Arrowsmith and A. Edwards for insightful discussions and/or constructive review of this manuscript and J. Lew, A. Hutchinson, A. Hassanali and H. Ren for their efforts in cloning and expressing the proteins in this study. The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from the Canadian Institutes for Health Research, the Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck & Co. Inc., the Novartis Research Foundation, the Petrus and Augusta Hedlund{\textquoteright}s Foundation, the Swedish Agency for Innovation Systems, the Swedish Foundation for Strategic Research and the Wellcome Trust. This work was also partially supported by a US National Institutes of Health grant (AI034036) to L.D.S.",
year = "2010",
month = may,
doi = "10.1038/nsmb.1795",
language = "English",
volume = "17",
pages = "596--601",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
number = "5",
}