Cellular copper management—a draft user's guide

Copper is essential to many organisms as a cofactor for many proteins and enzymes involved in key biological processes such as respiration and protection from oxidative stress. However, as copper is potentially toxic to living systems, regulatory mechanisms have evolved for its acquisition, trafficking, and release. These mechanisms, whose malfunction is typically associated with severe cellular damage, rely on the concerted action of protein systems that implement mechanisms for copper homeostasis and usage. The ensemble of copper proteins in given organisms can now be predicted with bioinformatics methods from an analysis of amino acid sequences. This work has endeavored to study the copper binding sites in these proteins, and to classify them based on their structural features. When associated with information on occurrence throughout the domains of life and intracellular localization, some generalized perspectives on copper management emerge that may provide a basis for the creation of models of cellular copper metabolism within a systems framework.