Identification of Methionine-rich Clusters That Regulate Copper-

Copper uptake and subsequent delivery to copper-de-pendent enzymes are essential for many cellular pro-cesses. However, the intracellular levels of this nutrient must be controlled because of its potential toxicity. The hCtr1 protein functions in high affinity copper uptake at the plasma membrane of human cells. Recent studies have shown that elevated copper stimulates the endocy-tosis and degradation of the hCtr1 protein, and this response is likely an important homeostatic mechanism that prevents the overaccumulation of copper. The do-mains of hCtr1 involved in copper-stimulated endocyto-sis and degradation are unknown. In this study we ex-amined the importance of potential copper-binding sequences in the extracellular domain and a conserved transmembrane 150MXXXM154 motif for copper-stimu