| Literature DB >> 20436473 |
Amy K Wernimont1, 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.
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.Entities:
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Year: 2010 PMID： 20436473 PMCID： PMC3675764 DOI： 10.1038/nsmb.1795
Source DB: PubMed Journal: Nat Struct Mol Biol ISSN： 1545-9985 Impact factor: 15.369