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Protons power protein portal to push zinc out of cells
Date:6/22/2014

Researchers at The Johns Hopkins University report they have deciphered the inner workings of a protein called YiiP that prevents the lethal buildup of zinc inside bacteria. They say understanding YiiP's movements will help in the design of drugs aimed at modifying the behavior of ZnT proteins, eight human proteins that are similar to YiiP, which play important roles in hormone secretion and in signaling between neurons.

Certain mutations in one of them, ZnT8, have been associated with an increased susceptibility to type 2 diabetes, but mutations that destroy its function seem to be protective.

A summary of the research will be published online in the journal Nature on June 22.

"Zinc is necessary for life. It requires transporter proteins to get into and out of cells, where it does its work," says Dax Fu, Ph.D., an associate professor of physiology. "If the transporter proteins malfunction, zinc concentrations can reach toxic levels. This study shows us how zinc-removing proteins work."

Zinc is needed to activate genes and to enable many proteins to function. In pancreatic beta cells, high concentrations of zinc are found inside the packages of insulin that they produce, although its precise role there is unknown.

YiiP is found partially embedded in the membranes of the bacterium E. coli, where it has a similar function to the ZnT human proteins. In a previous study, Fu's group mapped YiiP's atomic structure and found that there is a zinc-binding pocket in its center. But how a single pocket could transport zinc from one side of a membrane to the other was a mystery, he says.

Knowing that the protein lets one hydrogen ion or proton into the cell for every zinc ion it sends out, the team suspected there was a hidden channel that opened up to allow the ions to switch places.

To test this idea and to find out which inner segments of the protein make up the channel, the team collaborated
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Contact: Shawna Williams
shawna@jhmi.edu
410-955-8236
Johns Hopkins Medicine
Source:Eurekalert  

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