EXPLORING THE HUMAN COPPER METALLOCHAPERONE, ATOX1, DELIVERING PATHWAY

Metals are commonly found as natural constituents of proteins. However, many metal ions can be toxic when free in biological fluids. Hence, the human body has evolved tremendous sophistication and dedicates considerable regulatory machinery. Despite the high regulation of metal ions in the human body, diseases such as Menkes, Wilson, Alzheimer’s, Parkinson’s, and many other neurological disorders have been linked with copper/zinc/iron binding to proteins. Hence, it is tremendously important to understand each individual step of the metal cycle in the human body, in order to be able to recognize the origin of these neurological diseases and disorders. Nowadays, it is known that Cu(II) is accumulated in our body through diet, it is then reduced to Cu(I) and the copper transporter (CTR1) delivers it to the cell. When Cu(I) is transferred in to the cell, specific Cu(I) chaperones, are responsible for delivering it to specific cellular pathways. This work explores one aspect in the copper cycle, by probing the interaction between the human copper chaperone Atox1, and the CTR1 cytoplasmic loop and c-terminal domain, using Electron Paramagnetic Resonance (EPR) spectroscopy and Circular Dichroism (CD), upon coordinating to the metallochaperone Atox1. We show that C189 in CTR1 and, K60 and K38 of Atox1 are of great importance for proper interaction and transfer mechanism.