Calmodulin JMU: Difference between revisions

<Structure load='4lzx' size='350' frame='true' align='right' caption='Unbound Calmodulin' scene='Insert optional scene name here' />

Calmodulin (CaM), short for calcium modulated protein, is a small calcium binding protein with a three dimensional structure that allows calcium ions to come into the cells. Calcium is an essential mineral that is needed in the human diet for proper functioning of neurons, for the formation of strong bones, and to act as a second messenger for enzymes and proteins. Calmodulin is known to be involved in various Ca2+ - dependent signal transduction pathways, the protein act as a Ca2+ detector, and the protein is involved with regulating protein-kinases <ref>Eldik, L., & Watterson, D. (1998). Calmodulin and signal transduction</ref>.  

Its importance can be exemplified by the fact that the protein is known to be highly conserved in eukaryotes. Highly conserved structures that do not undergo significant evolutionary changes imply that the structure is mandatory for cell or organism survival and that any mutations in the genetic sequence that codes for the protein would be deleterious. The function of calmodulin is typically studied using yeast as a model organism. This is done for a variety of reasons, including the fact that yeast has a fully annotated genome with human homologues for genes associated with their ion channels, yeast is fast growing and yeast are heat stable<ref>Wolfe, D. M. D. M. (2006). Channeling studies in yeast: Yeast as a model for channelopathies?</ref>. Due to its ability to be easily manipulated, yeast can continue to be used to gather more information on calmodulins’ structure and function.

Calmodulin is located and used ubiquitously by cells, but is especially prevalent in brain and muscle tissue. It has also been found in human serum, breast milk, urine, and saliva<ref>MacNeil S., Dawson RA., Crocker G., Barton CH., Hanford L., McGurk MR., and Munro DS., (1988). Extracellular calmodulin and its association with epidermal growth factor in normal human body fluids.</ref>. Calmodulin in the cell is mainly localized within organelles and binds to Calcium. Calcium binding then promotes the phosphorylation of protein kinases and activation of other proteins to begin signal transduction for a variety of different pathways, mainly different forms of cell signaling. The phosphorylation of these protein-kinases occurs when Ca2+ reach about 1000 nM and initiates a rapid signaling pathway<ref>doi:10.1038/35036035</ref>.

Each end of the <scene name='71/716518/Globulardomain/1'>globular domains</scene> of CaM binds to two Calcium ions, which allows CaM to bind to a total of four Calcium ions. The conformational changes which CaM undergoes allow it to be able to bind more specifically (Figure 1). Calmodulin elicits a pathway signal transduction by activating protein kinases which can then go on to phosphorylate other proteins, or other proteins can directly bind to Calmodulin<ref>doi:  10.1128/EC.01.1.119-125.2002</ref>. This would require that the other proteins have a specific binding motif or substrate binding mechanism for Calmodulin (Figure 2). Because there are many different types of binding motifs used by other proteins to interact with Calmodulin, there are no conserved amino acid sequences for CaM binding. EF-hand motifs are a common type of calcium binding motif. These motifs can be characterized as having a helix-loop-helix pattern with 12 sequence residues. Aspartic acid, asparagine, glutamate, and serine are common residues found in this motif. By forming a loop, the motif allows calcium to bind more efficiently and securely (Figure 3). Once inside the binding site, calcium can then induce a conformational change.<ref>Lewit-Bentley, A., & Rèty S. (2000). EF-hand calcium-binding proteins. The Journal of current opinion in