3D-DATA COLLECTION FROM 2D-CRYSTALS OF THE HUMAN COPPER TRANSPORTER HCTR1

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. CTR-proteins are integral membrane proteins that mediate cellular copper uptake in all organisms except bacteria. Knock out studies have shown that CTR-proteins are essential for life, and recent genetic studies also identified CTR-proteins as the main entrance route for platinum based anti-cancer drugs. Despite their importance, very little is known about CTR-proteins, their structure and how their design facilitates translocation of copper and the structurally unrelated, much larger platinum compounds. Moreover, the mechanisms by which copper is loaded into the transporter and passed on to a collection of highly specific intracellular copper chaperons are mysterious at best. Our work is focused on determining the structure of the human high-affinity copper transporter hCTR1, embedded in a lipid bilayer, by electron crystallography, and to use our structural data to elucidate the mechanism by which hCTR1 interacts with other protein components.