Transport Tag Team

J. Am. Chem. Soc.

Heterocomplex between Atox1 (left) and WD. Copper is blue sphere, and critical lysine-60 residue is blue-tipped stick projection at upper right on Atox1.

A complex of two proteins forms transiently on the pathway that cells use to transport copper. The finding may have implications for understanding Cu-dependent diseases such as Wilson disease.

Cu is essential as an oxidation-reduction cofactor for cell processes. Too much of it is toxic, and too little causes anemia. To maintain a fine balance, cells have a complex system to traffic Cu, a process that is not fully understood. In one part of this system, Wilson disease protein (WD) exports Cu from cells after getting it from the copper-chaperone protein Atox1.

Now, Pernilla Wittung-Stafshede of Umeå University, in Sweden, and coworkers at Rice University show that Atox1-to-WD Cu delivery takes place via a Cu-bridged heterocomplex that the two proteins form transiently (J. Am. Chem. Soc., DOI: 10.1021/ja9058266). They find that one particular Atox1 residue, lysine-60, is essential for the complex to form and thus for Cu transfer to occur.

This is the first experimental verification that this particular protein-protein interaction occurs directly on the Cu-transfer pathway in cells, Wittung-Stafshede notes. "Computer simulations support the experimental data and reveal energetics for the heterocomplex," she says. "Better understanding of this Cu-transfer pathway mechanistically and chemically can eventually help human health."

Chemical & Engineering News

ISSN 0009-2347

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