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A contradictory protein readily accepts electrons despite having a strongly negative charge

A team of researchers at the Max Planck Institute for Medical Research made a striking discovery—a protein with contradictory properties: a strongly negative charge, yet a very high propensity for accepting electrons, which are also negative. This was unexpected, as negative charges normally repel each other.

The scientists determined the three-dimensional structure of the protein and found that there are positively charged calcium ions buried inside it, very near the place where the electrons are stored. The results show how nature can handle electric charges inside a protein and tune its properties.

Fascinating discovery

Energy flows through living cells in a variety of ways: one is by electrons moving along a series of protein molecules, as in an electric cable, passed from one protein to the next. While studying such proteins, researchers from the Max Planck Institute for Medical Research found an unusual version of cytochrome c.

Cytochrome c is a very common protein that transfers electrons from one protein to another. However, the newly discovered protein differs from "standard" cytochrome c in two ways. First, it has a much higher affinity for electrons than normal cytochrome c. Second, it has a strongly negative electric charge, whereas cytochrome c typically has a strong positive charge.

This combination of properties is unexpected, since a strong negative charge would normally make it more difficult for a protein to store electrons, as they are likewise negatively charged, and negative charges repel each other.

Calcium ions play a key role

This apparent contradiction intrigued Thomas Barends, research group leader at the Max Planck Institute for Medical Research. He and his team set out to investigate it—with surprising results. These have now been in the Journal of Biological Chemistry.

"It was fascinating to discover calcium ions so close to where the electrons are stored. It means that the protein keeps the electrons in a very advantageous place, because the positive charge of the calcium ions compensates the electrons' negative charge. This was surprising for us at first, since we had not seen calcium used in this way inside a protein before," explains Barends, a structural biologist.

According to the results, a calcium cation—a positively charged calcium ion—is located at a distance of less than 0.7 nanometers from the iron atoms the protein uses to store electrons. Even on the scale of molecules, that is very close.

"This arrangement could enable the protein to have a high affinity for electrons despite its negative charge, which we think it needs in order to bind to another protein to which it can pass the electrons at a later stage. In this way, it can optimally fulfill its biological function," concludes the team.

To prove that the calcium ions are actually the cause of the protein's high affinity for electrons, the Max Planck team studied the proteins with and without calcium and compared the data—no easy task, since calcium is a very common element and so contamination of the experiments was a constant problem.

At the same time, a group of theoretical chemists from the University of Bayreuth led by Matthias Ullmann carried out computer simulations, also with and without calcium. Their results confirmed the interpretation of the Max Planck team's data.

The new research findings provide a fine example of how nature resolves contradictions—in this case, by adjusting local electrical charges inside a protein so that its affinity for electrons is increased. This discovery is relevant both for understanding how energy flows through cells and also for developing new man-made proteins for nanotechnological applications.