Unknown

Dataset Information

0

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.

SUBMITTER: Wernimont AK 

PROVIDER: S-EPMC3675764 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Wernimont Amy K AK   Artz Jennifer D JD   Finerty Patrick P   Lin Yu-Hui YH   Amani Mehrnaz M   Allali-Hassani Abdellah A   Senisterra Guillermo G   Vedadi Masoud M   Tempel Wolfram W   Mackenzie Farrell F   Chau Irene I   Lourido Sebastian S   Sibley L David LD   Hui Raymond R  

Nature structural & molecular biology 20100502 5


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  ...[more]

Similar Datasets

| S-EPMC4568647 | biostudies-literature
| S-EPMC2718762 | biostudies-literature
| S-EPMC4050145 | biostudies-literature
| S-EPMC6628679 | biostudies-literature
| S-EPMC6952405 | biostudies-literature
| S-EPMC6185908 | biostudies-literature
| S-EPMC7337080 | biostudies-literature
| S-EPMC3336864 | biostudies-literature
| S-EPMC3049983 | biostudies-literature
| S-EPMC4974054 | biostudies-literature