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High-res view of zinc transport protein
Date:9/13/2009

solution of their x-ray vision by a mere angstrom (tenth of a nanometer). But because it brought the overall resolution of their structure to just below 3 angstroms the point at which individual atoms begin to become visible it enabled the scientists to see the protein in action as it bound to and transported zinc ions.

Using fluorescent probes, the scientists also studied how the protein changed shape in response to zinc binding. And they tested how changes to structural elements of the zinc transporter protein would affect its ability to transport zinc.

Together, these experiments suggest an auto-regulatory mechanism for zinc transport: Zinc binding within the cell triggers hinge-like movements of two electrically repulsive portions of the protein that lie within the cell's interior, which results in a conformational change in the portion of the protein that traverses the cellular membrane. So when zinc levels inside the cell rise too high, this shape shifting somehow pushes zinc ions through the membrane and out of the cell.

"Exactly how the protein pushes the zinc ions through the membrane has yet to be determined," said Fu, who added that this will be a focus of future research.

Conceivably, he added, drugs that bind to the zinc-sensing portions of the protein could be used to modulate zinc transport activity and help adjust zinc levels as possible treatments for diseases such as seizure disorders or diabetes. Brookhaven Science Associates, which manages Brookhaven Lab, has filed a patent application related to this work.

In addition, because other metal transporting proteins share similar architecture with the zinc transporter protein, the findings from this study may advance the understanding of other medical disorders linked to metal imbalance, as well as the development of possible treatments for those conditions.

Furthermore, this work may have implications for researchers trying to improve the prospe
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Contact: Karen McNulty Walsh
kmcnulty@bnl.gov
631-344-8350
DOE/Brookhaven National Laboratory
Source:Eurekalert

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