New Worlds: Solving a biological mystery

How do organisms living with arsenate pick and choose the right substance?

November 18, 2012 06:50
4 minute read.
Scientist at work (illustrative)

Scientist 311. (photo credit: Marretao22/Wikimedia Commons)

Some unassuming bacteria found themselves recently at the center of a scientific controversy: A group claimed that these microorganisms, which live in an environment rich in the arsenic-based compound arsenate, could take up that arsenate and use it – instead of the phosphate on which all known life on Earth depends. The claim, since disproved, raised another question: How do organisms living with arsenate pick and choose the right substance?

Chemically, arsenate is nearly indistinguishable from phosphate. Prof. Dan Tawfik of the Weizmann Institute of Science’s department of biological chemistry says, “Phosphate forms highly stable bonds in DNA and other key biological compounds, while bonds to arsenate are quickly broken. But how does a microorganism surrounded by arsenate distinguish between two molecules that are almost the same size and have identical shapes and ionic properties?”

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To investigate, Tawfik – along with postdoctoral fellow Dr. Mikael Elias, doctoral student Alon Wellner and lab assistant Korina Goldin, in collaboration with Tobias Erb and Julia Vorholt of ETH Zurich – looked at a protein in bacteria that takes up phosphate. This protein, called PBP (phosphate-binding protein), sits near the bacteria’s outer membrane, where it latches onto phosphates and passes them on to pumps that transport them into the cell.

In research that recently appeared in Nature, the team compared the activity of several different PBPs – some from bacteria like E. coli that are sensitive to arsenate and others, like those from the arsenic-rich environment, which are tolerant of the chemical.

While the PBPs in the ordinary bacterium were about 500 times more likely to bind phosphate over arsenate, in the arsenic-tolerant bacterium that factor jumped to around 5,000. In other words, to cope with their toxic environment, the bacteria evolved a mechanism of extreme selectivity to ensure their supply of phosphate while keeping the arsenate out.

Elias then compared phosphate and arsenate binding by crystallizing PBPs along with one of the two compounds. But the initial comparison suggested that when arsenate bound to the protein, it did so in just the same way as phosphate. Elias suspected that the key might lie in a single, highly unusual bond between a hydrogen atom in the protein and the molecule.

This bond had been previously noted but ignored, as phosphate binding occurred with or without it.

To see the difference, the team had to stretch the limits of crystallization technology, getting the resolution to less than one angstrom – fine enough to identify individual hydrogen atoms and compare their bonds. Only then were they able to identify a single disparity: The angles of that unusual hydrogen bond were different.

Inside a tight cavity within the PBP structure, phosphate binds at a “textbook angle,” according to Elias. The slightly larger arsenate molecule, on the other hand, gets pushed up against the hydrogen and bonds at unnatural, distorted angles. Tawfik thinks that the angle is likely to lead to repulsion between the molecule and other atoms in the cavity, preventing the PBP from passing arsenate into the cell’s interior.

Tawfik concluded: “These findings may go beyond the solving of a biological mystery.

Because phosphates are scarce in many environments, there is quite a bit of interest in understanding how this crucial resource is taken up by organisms. This first observation of a PBP discrimination mechanism is an exciting demonstration of the exquisite fine tuning that enables proteins to distinguish between two nearly identical molecules.”


Women who read negative news remember it better than men do and have stronger stress responses in subsequent stress tests, according to new research published recently in the journal PLOS ONE.

Scientists from the University of Montreal exposed groups of men and women to a succession of headlines drawn from recent newspaper articles. One group viewed only “neutral” news, while the other group was shown news perceived as “negative.” After reading the news, participants performed a standard psychological stress test. Researchers monitored participants’ stress levels during the process by measuring levels of cortisol, a stress hormone, in the saliva.

The authors found that, though reading negative news did not increase stress for any of their subjects, women exposed to negative news had higher cortisol levels after the psychological stress test exposure than did men who saw the same negative news, and also higher than either men or women who saw “neutral” news. In addition, one day later the women were more likely than the men to remember and experience emotional responses to the negative news they had viewed the previous day, according to the results of this study.

Though previous studies have assessed the role of continuous exposure to mass media as a stress factor, this is the first research that questions the effects of exposure to negative news coverage on stress reactivity and later recall of the news. The results of this study suggest that gender differences underlying the processes of stress and memory may play a role in how we react to negative news in the media.

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