Sensory Protein Modification

Abstract

How cells sense changes in copper ion concentration is a central question in copper-ion homeostasis. This is because the essential yet toxic biological nature of copper ions depends on its intracellular concentration. The importance of copper ions in living organisms is explained by its role as a cofactor for a number of enzymes involved in cellular physiology (1). Its toxic nature is generally thought to be the result of excess copper ions that can participate in reactions that generate reactive oxygen molecules such as O2 - and HO• (2). Copper ions might also displace other metal ions such as Zn2+ from their respective protein molecules, perturbing or disrupting their functions (3,4). Copper-ion exposure is also known to change the intracellular redox state (5), which may also trigger toxic effects. A recent investigation found higher mutation frequencies of the tumor suppressor p53 in Wilson’s disease patients who had accumulated excess copper ions in the liver and other organs (6). The presence of copper ions is necessary for the radiation of γ-rays to cause DNA conformational changes from a right-handed to a left-handed helical form (7). While avoiding an excessive accumulation of copper ions, cells must also prevent copper-ion deficiency that deprives the functions of copper-dependent enzymes, as is seen in Menkes syndrome patients (8–10). Clearly, in order to maintain a “just right” concentration, cells must have the ability to differentiate the physiological from the toxic copper level.