Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

High-res view of zinc transport protein

15.09.2009
Reveals shape-shifting atomic interactions; suggests mechanism and possible drug targets

How much difference can a tenth of a nanometer make? When it comes to figuring out how proteins work, an improvement in resolution of that miniscule amount can mean the difference between seeing where atoms are and understanding how they interact.

Case in point: New, improved-resolution views of a zinc transporter protein deciphered at the U.S. Department of Energy's Brookhaven National Laboratory provide not just a structure but also a suggested mechanism for how cells sense and regulate zinc, an element that is essential for life, but which must be kept at a steady state to avoid problems like seizures, diabetes, and possibly Alzheimer's disease.

The new findings, to be published online on September 13, 2009, by Nature Structural & Molecular Biology, also suggest targets for zinc-regulating drugs, and may even advance the understanding of similar zinc-regulating enzymes in plant chloroplasts with possible implications for biofuel production.

"Our goal is to reveal atomic interactions in a protein structure to understand the chemistry that underlies the protein's biological function," said Brookhaven biologist Dax Fu, who led the research. "With this structure, we can begin to understand the mechanism of zinc transport at a chemical level."

The structure was revealed using x-ray crystallography at Brookhaven Lab's [http://www.nsls.bnl.gov/] National Synchrotron Light Source (NSLS), a source of intense x-ray, ultraviolet, and infrared light. By studying how x-rays bounce off crystallized samples of a protein, scientists can reconstruct the location and orientation of the protein's atoms in three dimensions.

The Brookhaven team had previously used NSLS to solve a zinc transporter protein structure at lower resolution*. To achieve the new-and-improved structure, the scientists added mercury atoms to stabilize protein packing in the crystals. This increased the resolution 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 prospects of biomass production in plants, an essential component to the development of biofuels. Zinc is an essential co-factor in a host of reactions in chloroplasts, the site of photosynthesis. But as is the case in animals, excess metals can be highly toxic in plants. Consequently, studies to help elucidate zinc-transporter protein function could help scientists understand how plants maintain the delicate balance needed for ideal growth.

Future studies of protein structures at Brookhaven Lab promise to reveal even greater mechanistic detail when a new light source, known as NSLS-II, opens in 2015. That facility, now under construction, will be 10,000 times brighter than NSLS. That boost in brightness — and therefore resolution — would be particularly important in the study of membrane proteins, which represent the vast majority of proteins of interest to those developing drugs, but which are also often difficult to crystallize.

"As illustrated by this study, even small improvements in x-ray diffraction resolution can greatly advance our mechanistic understanding of protein function," said Fu.

This research was performed at beamline X25A at the NSLS. The work was supported by the National Institutes of Health, DOE's Office of Science (Office of Basic Energy Sciences), and by the Biology Department at Brookhaven Lab.

Related Links

* Previous News Release: Zinc Transporter Protein Structure Deciphered: http://www.bnl.gov/bnlweb/pubaf/pr/PR_display.asp?prID=07-89

One of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. Brookhaven is operated and managed for DOE's Office of Science by Brookhaven Science Associates, a limited-liability company founded by the Research Foundation of State University of New York on behalf of Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.

Visit Brookhaven Lab's electronic newsroom for links, news archives, graphics, and more: http://www.bnl.gov/newsroom

Karen McNulty Walsh | EurekAlert!
Further information:
http://www.bnl.gov
http://www.bnl.gov/bnlweb/pubaf/pr/PR_display.asp?prID=07-89
http://www.bnl.gov/newsroom

More articles from Life Sciences:

nachricht Brought to light – chromobodies reveal changes in endogenous protein concentration in living cells
21.09.2018 | NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen

nachricht A one-way street for salt
21.09.2018 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Scientists present new observations to understand the phase transition in quantum chromodynamics

The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.

This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.

Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...

Im Focus: Patented nanostructure for solar cells: Rough optics, smooth surface

Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.

"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...

Im Focus: New soft coral species discovered in Panama

A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.

Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...

Im Focus: New devices based on rust could reduce excess heat in computers

Physicists explore long-distance information transmission in antiferromagnetic iron oxide

Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.

Im Focus: Finding Nemo's genes

An international team of researchers has mapped Nemo's genome

An international team of researchers has mapped Nemo's genome, providing the research community with an invaluable resource to decode the response of fish to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

"Boston calling": TU Berlin and the Weizenbaum Institute organize a conference in USA

21.09.2018 | Event News

One of the world’s most prominent strategic forums for global health held in Berlin in October 2018

03.09.2018 | Event News

4th Intelligent Materials - European Symposium on Intelligent Materials

27.08.2018 | Event News

 
Latest News

Astrophysicists measure precise rotation pattern of sun-like stars for the first time

21.09.2018 | Physics and Astronomy

Brought to light – chromobodies reveal changes in endogenous protein concentration in living cells

21.09.2018 | Life Sciences

"Boston calling": TU Berlin and the Weizenbaum Institute organize a conference in USA

21.09.2018 | Event News

VideoLinks
Science & Research
Overview of more VideoLinks >>>