Structural domains overview |
Shown below is an overview of all the structural domains of CaMKIV. CaMKIV is a kinase enzyme which contains 4 major functional domains. Details regarding all the major CaMKIV domains can be accessed via the pannel to the left (under page index). |
The function of CaMKIV is critically dependent on the expression of the four domains (see pannel to the left). Abnormal function in any one of the four domains could lead to disease and pathology within the immune or nervous system. For example, a loss of function mutation within the ATP binding residues of the Catalytic domain can lead to constituent CaMKIV inactivation even in the face of high levels of activating signals (in form of Calcium/Calmodulin complex), as ATP can no longer bind to the mutated ATP binding residue and phosphorylation cannot occur as a result. In contrast, a loss-of-function mutation in the autoinhibitory domain could lead to constitutive CaMKIV activation by permanently abolishing the binding between this domain and PP2A. However, bear in mind that the mutations within these regions are NOT the only ways that could affect the activity of the CaMKIV signalling cascade. For example, a mutation in the CRAC channel (please see introduction) could lead to constituve influx of calcium, as a result the Calcium/Calmodulin binding complex within the affected cells always stay at a high concentration, which could also lead to constituve activation of CaMKIV. It is also worth noting that there will probably be other side effects associated with such a mutation, which could again influence the behaviour of the CaMKIV signalling pathway in an indirectly way. |
Structural comparison between CaMKIV from PDB and predicted CaMKIV |
Left: CaMKIV structure obtained from PDB Middle: Superimposition of the left and right images, the red regions represent flexible parts of the protein which cannot be visualised using crystallography (due to their dynamic nature) Right: Predicted model obtained using Swissmodel |
Sequence comparison between the predicted CaMKIV and CaMKIVα |
The 3D model we obtained using SwissModel is only a fragment of the 473-amino-acid-long CaMKIV isoform α (NCBI accession code: EAW49034.1). The template used is the PDB file 2w4o. While modelled residues are shown in blue below (34-337), the crossed out sequences represents the amino acids on CaMKIVα that are not present in the predicted 3D model. |
References for Predicted CaMKIV (Swissmodel) |
[1] Arnold K., Bordoli L., Kopp J., and Schwede T. (2006). The SWISS-MODEL Workspace: A web-based environment for protein structure homology modelling. Bioinformatics, 22,195-201. |
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