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

被引：179

作者：

Wernimont, Amy K. ^{[1
]}

Artz, Jennifer D. ^{[1
]}

Finerty, Patrick, Jr. ^{[1
]}

Lin, Yu-Hui ^{[1
]}

Amani, Mehrnaz ^{[1
]}

Allali-Hassani, Abdellah ^{[1
]}

Senisterra, Guillermo ^{[1
]}

Vedadi, Masoud ^{[1
]}

Tempel, Wolfram ^{[1
]}

Mackenzie, Farrell ^{[1
]}

Chau, Irene ^{[1
]}

Lourido, Sebastian ^{[2
]}

Sibley, L. David ^{[2
]}

Hui, Raymond ^{[1
]}

机构：

[1] Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada

[2] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2010年 / 17卷 / 05期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

CALMODULIN-LIKE DOMAIN; PLASMODIUM-FALCIPARUM; CDPK; AUTOPHOSPHORYLATION; FEATURES; COMPLEX; ASSAY;

D O I：

10.1038/nsmb.1795

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：596 / U95

页数：7

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