Structural genomics of proteins involved in copper homeostasis

Genome sequencing projects have provided a wealth of data, most notably the primary sequences of all the proteins that a given organism can produce. The understanding of this information at the functional level is still in the beginning stages. Three-dimensional structural information is necessary to unravel at the atomic level the mechanisms by which a protein carries out its function, and such information can often be very useful to predict at least gross functional features, even in the absence of biochemical data. An exhaustive structural characterization of the proteins encoded in the genomes is thus highly desirable. To enhance the functional insights provided by genome-scale structural determination, we have prioritized our research to target specific processes of the cell, i.e., those responsible for controling metal homeostasis. In this Account, we present the results obtained by the Magnetic Resonance Center of the University of Florence on proteins involved in the homeostasis of copper. The general research strategy is presented, followed by a discussion focused on different key experimental aspects. An overview of the initial results and of their relevance to the understanding of molecular function and cellular processes is also given.