Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Protons power protein portal to push zinc out of cells


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:

Fu Lab:

Shawna Williams | Eurek Alert!

Further reports about: Medicine hydroxyl protons radicals segments zinc

More articles from Life Sciences:

nachricht High-arctic butterflies shrink with rising temperatures
07.10.2015 | Aarhus University

nachricht Long-term contraception in a single shot
07.10.2015 | California Institute of Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Kick-off for a new era of precision astronomy

The MICADO camera, a first light instrument for the European Extremely Large Telescope (E-ELT), has entered a new phase in the project: by agreeing to a Memorandum of Understanding, the partners in Germany, France, the Netherlands, Austria, and Italy, have all confirmed their participation. Following this milestone, the project's transition into its preliminary design phase was approved at a kick-off meeting held in Vienna. Two weeks earlier, on September 18, the consortium and the European Southern Observatory (ESO), which is building the telescope, have signed the corresponding collaboration agreement.

As the first dedicated camera for the E-ELT, MICADO will equip the giant telescope with a capability for diffraction-limited imaging at near-infrared...

Im Focus: Locusts at the wheel: University of Graz investigates collision detector inspired by insect eyes

Self-driving cars will be on our streets in the foreseeable future. In Graz, research is currently dedicated to an innovative driver assistance system that takes over control if there is a danger of collision. It was nature that inspired Dr Manfred Hartbauer from the Institute of Zoology at the University of Graz: in dangerous traffic situations, migratory locusts react around ten times faster than humans. Working together with an interdisciplinary team, Hartbauer is investigating an affordable collision detector that is equipped with artificial locust eyes and can recognise potential crashes in time, during both day and night.

Inspired by insects

Im Focus: Physicists shrink particle accelerator

Prototype demonstrates feasibility of building terahertz accelerators

An interdisciplinary team of researchers has built the first prototype of a miniature particle accelerator that uses terahertz radiation instead of radio...

Im Focus: Simple detection of magnetic skyrmions

New physical effect: researchers discover a change of electrical resistance in magnetic whirls

At present, tiny magnetic whirls – so called skyrmions – are discussed as promising candidates for bits in future robust and compact data storage devices. At...

Im Focus: High-speed march through a layer of graphene

In cooperation with the Center for Nano-Optics of Georgia State University in Atlanta (USA), scientists of the Laboratory for Attosecond Physics of the Max Planck Institute of Quantum Optics and the Ludwig-Maximilians-Universität have made simulations of the processes that happen when a layer of carbon atoms is irradiated with strong laser light.

Electrons hit by strong laser pulses change their location on ultrashort timescales, i.e. within a couple of attoseconds (1 as = 10 to the minus 18 sec). In...

All Focus news of the innovation-report >>>



Event News

EHFG 2015: Securing healthcare and sustainably strengthening healthcare systems

01.10.2015 | Event News

Conference in Brussels: Tracking and Tracing the Smallest Marine Life Forms

30.09.2015 | Event News

World Alzheimer`s Day – Professor Willnow: Clearer Insights into the Development of the Disease

17.09.2015 | Event News

Latest News

NASA provides an infrared look at Hurricane Joaquin over time

08.10.2015 | Earth Sciences

Theoretical computer science provides answers to data privacy problem

08.10.2015 | Information Technology

Stellar desk in wave-like motion

08.10.2015 | Physics and Astronomy

More VideoLinks >>>