Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protons power protein portal to push zinc out of cells

23.06.2014

Protein, linked to type 2 diabetes, prevents zinc toxicity

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.


The twisting (blue arrows) of the red portion of the zinc ion channel allows the opening and closing of its gate. Left: the channel is open to the inside of the cell, allowing zinc (green) to flow into its binding site (pink star) after hydrogen flows out. Right: the channel is open to the outside of the cell, allowing zinc to flow out and hydrogen to flow in.

Credit: Fu Lab, Johns Hopkins Medicine

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.

... more about:
»Medicine »hydroxyl »protons »radicals »segments »zinc

"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 with scientists at Brookhaven National Laboratory to shine intense X-rays at the protein while it was immersed in water. The X-rays caused the water molecules to split into two components: hydrogen atoms and hydroxyl radicals. When the hidden channel within the protein opened up, the hydroxyl radicals bonded with the exposed protein segments, "marking" the ones that created the channel.

The researchers then cut up YiiP using enzymes and analyzed the resulting pieces in an instrument that helped them identify the makeup of each piece. By comparing those pieces to pieces of YiiP that had not been exposed to hydroxyl radicals, the researchers could tell which segments create the channel.

Using this and other information, the scientists were able to figure out how the protein works.

Outside the membrane is an abundance of protons, with a lower concentration inside the membrane, creating what is known as a concentration gradient. The protons want to flow "down" this gradient into the cell, like water following gravity down a waterfall, says Fu. Thus, when the central pocket of the transporter protein is open to the outside, a proton will bind to the pocket.

"When the protons move from a place of high concentration to low concentration, they generate a force like falling water does," he says. The protein harnesses this force to change its shape, cutting off the pocket's access to the outside environment and opening up its access to the inside. There, the proton will continue its "fall" by unbinding from the pocket and entering the inside space.

Once it has released the proton, the pocket is free to bind to zinc. This binding again changes the protein's shape, shutting off the pocket's access to the inside of the membrane and once again exposing it to the outside. A proton then drives the zinc ion out of the pocket, and the cycle continues.

"Understanding the way the protein works, especially which segments of the protein do what, will help us design better drugs to moderate its activity wherever it is found," says Fu.

###

Other authors of the report include Jie Cheng of the Johns Hopkins University School of Medicine; Sayan Gupta, Rhijuta D'Mello and Mark Chance of Case Western Reserve University; and Jin Chai of Brookhaven National Laboratory.

This work was supported by grants from the National Institute of General Medical Sciences (R01GM065137), the National Institute of Biomedical Imaging and Bioengineering (P30-EB-09998, R01-EB-09688), and the U.S. Department of Energy (KC0304000, DE-AC02-98CH10886).

On the Web:

Link to article: http://dx.doi.org/10.1038/nature13382

Fu Lab: http://fulab.johnshopkins.edu/

Shawna Williams | Eurek Alert!

Further reports about: Medicine hydroxyl protons radicals segments zinc

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>