Structural highlights
Function
[CDPK1_ARATH] May play a role in signal transduction pathways that involve calcium as a second messenger. Phosphorylates the Ca(2+)-ATPase ACA2 resulting in the inhibition of its calcium activation.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Calcium-dependent protein kinases (CDPKs) are a class of calcium-binding sensory proteins that are found in plants and certain protozoa, including the causative agent of malaria, Plasmodium falciparum. CDPKs have diverse regulatory functions, including involvement in the triggering of the lytic cycle of malarial infection. CDPKs contain an autoinhibitory junction (J) region whose calcium-dependent interaction with the tethered regulatory calmodulin-like domain (CaM-LD) activates the catalytic kinase domain. We report here the X-ray crystal structure of the J-CaM-LD region of CDPK from Arabidopsis thaliana (AtCPK1), determined to 2.0 A resolution using multiple-wavelength anomalous dispersion (MAD). The structure reveals a symmetric dimer of calcium-bound J-CaM-LD with domain-swap interactions, in which the J region of one protomer interacts extensively with the carboxy-terminal EF-hand domain (C-lobe) of the partner protomer. However, as the J-CaM-LD is monomeric in solution, the activated monomer was modelled to account for the intra-molecular recognition of the two domains. While the J-CaM-LD segment mimics certain aspects of target motif recognition by CaM other features are specific to CDPKs, in particular the combination of the strong interaction between the N and C-lobes of the CaM-LD and the exclusive use of only the C-lobe in the recognition of the covalently tethered target region. Combined with our previous observations showing that there is likely to be strong interactions between this tethered J region and the CaM-LD even at basal Ca(2+) concentrations, the new structural data indicate that the response to calcium of CDPKs is clearly unique among the CaM family.
Structure of the regulatory apparatus of a calcium-dependent protein kinase (CDPK): a novel mode of calmodulin-target recognition.,Chandran V, Stollar EJ, Lindorff-Larsen K, Harper JF, Chazin WJ, Dobson CM, Luisi BF, Christodoulou J J Mol Biol. 2006 Mar 24;357(2):400-10. Epub 2005 Dec 20. PMID:16430916[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Harper JF, Huang JF, Lloyd SJ. Genetic identification of an autoinhibitor in CDPK, a protein kinase with a calmodulin-like domain. Biochemistry. 1994 Jun 14;33(23):7267-77. PMID:8003490
- ↑ Huang JF, Teyton L, Harper JF. Activation of a Ca(2+)-dependent protein kinase involves intramolecular binding of a calmodulin-like regulatory domain. Biochemistry. 1996 Oct 8;35(40):13222-30. PMID:8855961 doi:http://dx.doi.org/10.1021/bi960498a
- ↑ Vitart V, Christodoulou J, Huang JF, Chazin WJ, Harper JF. Intramolecular activation of a Ca(2+)-dependent protein kinase is disrupted by insertions in the tether that connects the calmodulin-like domain to the kinase. Biochemistry. 2000 Apr 11;39(14):4004-11. PMID:10747788
- ↑ Hwang I, Sze H, Harper JF. A calcium-dependent protein kinase can inhibit a calmodulin-stimulated Ca2+ pump (ACA2) located in the endoplasmic reticulum of Arabidopsis. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6224-9. PMID:10823962
- ↑ Chandran V, Stollar EJ, Lindorff-Larsen K, Harper JF, Chazin WJ, Dobson CM, Luisi BF, Christodoulou J. Structure of the regulatory apparatus of a calcium-dependent protein kinase (CDPK): a novel mode of calmodulin-target recognition. J Mol Biol. 2006 Mar 24;357(2):400-10. Epub 2005 Dec 20. PMID:16430916 doi:10.1016/j.jmb.2005.11.093
