Previously, we have solved the structures of calcium-dependent protein kinases (CDPK) from Cryptosporidium parvum and Toxoplasma gondii, which enabled us to propose a mechanism of activation of this subfamily of kinases by calcium [1, 2, 3]. CDPKs are also found in Plasmodium parasites. Specifically, Plasmodium CDPK1 is implicated in host invasion, CDPK3 in transmission, CDPK4 in gamete formation and transmission and CDPK5 in egress of the parasite from erythrocytes.

We present here the structure of the calcium-bound (hence activated) form of CDPK1 from Plasmodium berghei, which is > 70% identical in sequence to its orthologue from Plasmodium falciparum. Like the calcium-bound structures of Toxoplasma and Cryptosporidium CDPKs (e.g. PDB ID: 3HX4, 3IGO, 3LIJ), the regulatory domain known as the CAD domain is located on the side of the kinase domain away from the active site.

References

1. Wernimont AK, Amani M, Qiu W, Pizarro JC, Artz JD, Lin YH, Lew J, Hutchinson A, Hui R. Structures of parasitic CDPK domains point to a common mechanism of activation. Proteins. 2011 Mar;79(3):803-20.
2. Wernimont AK, Artz JD, Finerty P Jr, Lin YH, Amani M, Allali-Hassani A, Senisterra G, Vedadi M, Tempel W, Mackenzie F, Chau I, Lourido S, Sibley LD, Hui R. Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium. Nat Struct Mol Biol. 2010 May;17(5):596-601.
3. Artz JD, Wernimont AK, Allali-Hassani A, Zhao Y, Amani M, Lin YH, Senisterra G, Wasney GA, Fedorov O, King O, Roos A, Lunin VV, Qiu W, Finerty P Jr, Hutchinson A, Chau I, von Delft F, MacKenzie F, Lew J, Kozieradzki I, Vedadi M, Schapira M, Zhang C, Shokat K, Heightman T, Hui R. The Cryptosporidium parvum kinome. BMC Genomics. 2011 Sep 30;12:478.