Fig. 2.

Structure and Ca²⁺-mediated activation of a calmodulin-like domain protein kinase. a The figure depicts the X-ray crystallographic structure of Ca²⁺-dependent protein kinase 1 (AtCDPK1) from Arabidopsis thaliana at 2 Å resolution (Q06850 CDPK1_ARATH based on template 4m97A, residue range 142–588) taken from UniProt SWISS-MODEL database. The crystallographic structure in the left panel is shown using a rainbow color code going from the N-terminal (blue) to the C-terminal (red). The Ca²⁺-binding sites in the four EF-hands are highlighted in the right panel in different colors indicating the amino acid residues involved. b The figure depicts a model for the Ca²⁺-dependent activation of a CaM-like domain protein kinase (CDPK). In the absence of Ca²⁺, a non-physiological condition, when the four EF-hands of the CDPK are free of Ca²⁺ (apo-CDPK), a sector of the junction domain (JD) blocks the catalytic site of the protein kinase (PK) rendering the enzyme inactive (top panel). In basal conditions, when the cytosolic Ca²⁺ concentration is very low (< 50–100 nM) the high-affinity Ca²⁺-binding sites located in the distal EF-hands 3 and 4 are occupied and both of them interact with the JD (marked in green), the catalytic site is partially released and the enzyme becomes partially active (central panel). The interrogation mark indicates a discrepancy in the literature as to whether binding of Ca²⁺ to EF-hands 3 and 4 is sufficient to at least partially release the auto-inhibition (see references [27–31]). When the cytosolic Ca²⁺ concentration increases at saturating concentrations (> 0.5–1 µM), the two low-affinity Ca²⁺-binding sites located in EF-hands 1 and 2 are also occupied by Ca²⁺, and all EF-hands interact with the JD (marked in green) which is totally released from the catalytic site rendering the enzyme fully active (bottom panel). Ca²⁺ ions are represented by gray spheres. CaM-LD calmodulin-like domain.

Partially based on references [31, 36]