Within in the cell, calcium signaling is accompanied by a temporary increase in the concentration of calcium ions, which is sensed by proteins such as calmodulin (Bertini et.
The concentration of these ions must be closely regulated.
To understand the thermodynamics that couples the activation of calmodulin, one must first understand the concentration of ions such as calcium and magnesium within a eukaryotic cell, including that of a human. This is related to the thermodynamics of calmodulin within the cell and how it responds to the presence of calcium ions. This conformation may lend an idea of why calmodulin is selective for calcium and how only the presence of a calcium ion can satisfy the binding site that causes the protein to activate. One can notice that the EF motif within calmodulin includes many of the same ligands, just in different places. The binding site of calmodulin consist of a Ca 2+ ion surrounded by 6 ligands while forming 7 bonds. The 6 ligands of calmodulin include the side chains of three asparatic acids (D), 1 glutamic acid (E) that forms two coordinate covalent bonds with the ion, 1 water molecule from solution, and 1 carbonyl molecule from the backbone. The calmodulin binding site is somewhat different than the most typical EF hand domain shown above. The dashed line represents coordination of Ca to the oxygen of a backbone carbonyl, while solid lines indicate coordination to side chains or water. This cartoon illustrates the coordinated amino acids in a typical EF hand domain (The exact amino acid composition varies!). The typical EF-hand domain bonding sequence is shown in the figure below. In a characteristic EF-hand motif, amino acids including glutamates, asparagines, aspartic acids, and glutamic acids bind to Ca, as well as water (Bertini et. This is demonstrated in the figure above. These regions are known as “hand” motifs because they resemble a hand that is made in the shape of an L, where the metal ion is located in the middle of the fist, the alpha helices are indicated by the upward-pointing index finger and inward-facing thumb, and the curled fingers represent the turn or loop region.
#Overall charge of calcium code#
(PDB code 3CLN)ĮF-hand motifs are highly conserved structural regions of proteins involved in the binding of calcium. The ribbon diagram on the left shows one of the four characteristic helix-turn-helix EF hand motifs of calmodulin. This image is a depiction of how an EF-hand motif resembles a hand. Based on its structure and its need for calcium ions to function, calmodulin must be able to select for calcium ions in the cytoplasm, and the interactions between the ion and the ligands in the EF hand domains support this idea of selectivity (Bertini et. Coined for its flexibility, the central tether region is the location of the protein on which partner proteins bind and contribute to the cascade that is the secondary messaging of calcium. When calmodulin binds with the calcium ions, the protein opens from its apo form to its halo form, exposing an alpha helix that is known as the linker or central tether region. When activated, calmodulin houses 4 Ca 2+ ions that drastically change the shape of the protein.
The protein itself is 148 amino acids in length with two globular regions containing 2 EF-hand motifs each, which are characteristic sites of calcium-mediated polypeptides.
0 kommentar(er)
