A study to be published as the “Paper of the Week” in the Journal of Biological Chemistry this December details how zinc, an element fundamental to cell growth, enters the cell via zinc-specific uptake proteins. The research, conducted at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory, is the first to purify this kind of protein and study its role in zinc uptake.
Zinc is crucial to the health of all living organisms. At the cellular level, zinc is responsible for cell growth, which in turn affects the health, growth, and reproduction of an organism.
While there are six classes of known proteins that act as transporters or channels enabling zinc to cross the cell membrane, scientists have identified one metal-specific family of proteins whose purpose is to facilitate the cell’s zinc uptake. These are called ZIP proteins, a reference to their resemblance to zinc-regulated and ion-regulated transporter proteins.
The exact mechanism by which ZIP proteins facilitate zinc uptake has been a mystery. Brookhaven scientists led by biologist Dax Fu — who have characterized other zinc-specific proteins that maintain healthy levels of zinc on either side of the cell membrane* — have now taken a closer look at this process.
A long-held belief has posited that ZIP proteins work like elevators, pumping zinc across the cell membrane and into the cell. However, Fu and his colleagues found no evidence to support this explanation.
“This was a big surprise. For the last fifteen years, the assumption has been that the ZIP protein acts like a pump or elevator,” said Fu. “Instead, we have found that ZIP is more like a door.”
Fu and his colleagues have studied a ZIP protein provided by the New York Consortium on Membrane Protein Structure and derived from the bacteria Bordatella bronchiseptica. They expressed the protein in Eschericia coli, a bacteria whose zinc regulation has been well documented. Brookhaven’s Jin Chai purified and concentrated the samples before exposing them to zinc. By reconstituting the purified ZIP proteins in this controlled manner, the scientists ensured that their sample would reflect only the ZIP mechanism for cellular zinc uptake.
“It’s important to note that people have been trying to purify these proteins for a long time. Purification of the first ZIP family member opens the door for detailed structural and functional analysis at the molecular level,” Fu said.
Using a fluorescent indicator, Brookhaven’s Wei Lin then conducted several measurements to characterize zinc uptake, with attention to changes in zinc concentration, temperature, acidity, and electric charge.
The Brookhaven team found evidence of electrodiffusion. Ions diffuse by moving from a region with a high concentration to one of a lower concentration — like diners who relocate from a crowded dining hall to an adjoining, empty coffee room. In electrodiffusion, the diffused ions also change the electric charge of the space that they occupy. The imbalance in charge created by zinc ions moving into the cell builds during zinc uptake and acts against the concentration gradient, eventually causing zinc uptake to stop.
Based in part on the studies of similar metal-specific proteins, Fu and his colleagues have postulated that the ZIP protein allows zinc ion diffusion by providing an opening that is specifically shaped for zinc coordination chemistry. This hypothesis will eventually be confirmed in studies that crystallize and examine the ZIP protein at the atomic level.
“We are driven by our curiosity — we want to know how this works,” Fu said.
Aside from satisfying scientific curiosity, this understanding could have a big impact. Zinc uptake at the cellular level is implicated in a range of biomedical and energy research. For example, in green plants, carbonic acid is converted to CO2 in a chemical reaction that is catalyzed by a zinc enzyme.
Zinc deficiency, therefore, has a direct impact on the carbohydrate metabolism of plants. For researchers developing biofuels energy sources, these systems and the role of zinc transporters in the conversion of energy into carbohydrates, are important objects of study. Developing a better understanding of zinc uptake can provide greater insight into these processes and will inform future discoveries.
In addition to the Brookhaven researchers, James Love of the New York Structure Biology Center contributed to this research. Funding and support for the work came from the DOE Office of Science and from the National Institutes of Health.
Karen McNulty Walsh | EurekAlert!
Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington
The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie
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,...
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...
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...
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...
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...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
17.08.2017 | Physics and Astronomy
17.08.2017 | Earth Sciences
17.08.2017 | Physics and Astronomy