Toxoplasma gondii CDPK1, TGME49_101440, in presence of calcium
Wernimont, A.K., Artz, J.D., Finnerty, P., Lin, Y.H., Amani, M., Schapira, M., Allali-Hassanali, A., Vedadi, M., Tempel, W., MacKenzie, F., Hui, R.
(deposited on 24.Jun.09)
Datapack version: 1 (built on 02.Oct.09; last revised in 02.Oct.09)
Calcium controls various essential pathways in apicomplexan parasites including protein secretion, motility, host invasion and egress. To mediate calcium pathways, these organisms employ calcium-dependent protein kinases (CDPK), which are also found in plants and ciliates but not in animals or fungi.
– the parasite responsible for transmission of toxoplasmosis – has a number of CDPKs in its genome, with both TgCDPK1 and TgCDPK3 characterized in previous studies[1,2].
Canonical CDPKs are comprised of a kinase domain (KD) that is highly homologous to calmodulin-dependent kinases (CaMK), followed by 4 EF-hands, which bind Ca
and play the role of intramolecular regulation. We call this regulatory domain the CDPK activation domain (CAD).
Here, we present the structure of
intact. This structure represents the general activated form of a canonical CDPK.
in the CAD has a Ca
bound. As found with calmodulin, binding of calcium opens up each EF-hand, exposing hydrophobic surfaces and resulting in a refolding of CAD. The extent of refolding can be seen by comparing this structure against that of
, which is in the inhibited conformation. Furthermore, we can also see that the CAD
has translocated to
a new location relative to the KD, away from the substrate binding site and therefore allowing it to become active.
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, which is
a single long helix
in the inhibited conformation (3HZT), is bent into
in this activated conformation. The same is also true of the
. The two are intertwined around each other, in addition to interaction with the two EF-lobes.
In its new position, the refolded CAD interacts with the KD via various
. Most interestingly,
a stretch of residues
) in the N-terminus of the KD latches into a cleft in the CAD.
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Kieschnick H, Wakefield T, Narducci CA, Beckers C (2001) Toxoplasma gondii attachment to host cells is regulated by a calmodulin-like domain protein kinase. J Biol Chem 276: 12369-12377.
Nagamune K, Sibley LD (2006) Comparative genomic and phylogenetic analyses of calcium ATPases and calcium-regulated proteins in the apicomplexa. Mol Biol Evol 23: 1613-1627.
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