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Cut and dried: How proteins stay active without water


07 April 2021

by: Heinz Maier-Leibnitz Zentrum, 7 April 2021

Normally, proteins need water in order to function properly. Using neutrons to examine them more closely, scientists have observed how they can also function without water, and how the oxygen-transporting muscle protein myoglobin is able to still move around. Their results have now been published in the renowned journal Physical Review Letters.

Until recently, it was widely accepted that proteins need water. Without a liquid element as a lubricant, they cannot move, and thus cannot become active, according to prevailing opinion. But in 2010, researchers found that multichain molecules, known as polymers, also breathe life into proteins. This is interesting for many applications in medicine and cosmetics. However, it was previously unclear exactly how this works.

MyoglobinThe muscle protein myoglobin is colored red in this graph, the polymers purple. The rising bubbles symbolize oxygen released from myoglobin when the oxygen concentration falls below a threshold.
Copyright: Warwick Bromley

Film in picosecond resolution

Now, an international team of researchers led by Dr. Martin Weik of the Institut de Biologie Structurale at the University of Grenoble, France, have used neutrons at the Heinz Maier-Leibnitz Zentrum (MLZ) to see how proteins with polymers move compared to how they do so in an aqueous solution.

"We measured this roughly for the first time ten years ago. At that time, we were able to show that the protein moves and thus still functions, even though the water is gone." explains Martin Weik. "Now we are trying to understand exactly how these movements take place." For the more detailed measurements on the oxygen-transporting muscle protein myoglobin, the group again used the SPHERES backscattering spectrometer, operated by Forschungszentrum Jülich at the MLZ, but this time also carried out measurements at the TOFTOF time-of-flight spectrometer, operated by the Technical University of Munich (TUM).

"Here we can follow the movements of the myoglobin and polymers, which are distinctly labelled, down to a time scale of picoseconds," says Dr. Wiebke Lohstroh, instrument scientist and leading researcher at the TUM’s TOFTOF instrument. This is because neutrons reveal the movements of hydrogen atoms more clearly than those of heavier deuterium, which is used as a marker. The extended measurements at SPHERES have also made a crucial contribution: "Now the high-resolution spectra have been measured, it is possible to observe various motion processes directly at the molecular level," says Dr. Michaela Zamponi, instrument scientist at SPHERES from the Jülich Centre for Neutron Science (JCNS).

Polymer mimics movement of water

"With these results, we are able to make a concrete suggestion on what to improve in the polymer to make the protein even more active," says Martin Weik. "Surprisingly, we found that the polymer mimics movements of water." This keeps the dry protein biologically active, but certain movements are suppressed. This helps the researchers explain why the protein is less active when the water is replaced by polymers. With a little fine-tuning, however, it is possible to make the protein more active.

LohstrohDr. Wiebke Lohstroh at the TUM neutron time-of-flight spectrometer TOFTOF, which was able to resolve the motion of the protein-polymer compounds on a time scale of picoseconds.
Copyright: Andreas Heddergott

Heart patients benefit

The knowledge gained from this study is useful for the development of next-generation cell therapies for treating cancer or regeneration after heart attacks. The aim of the scientists is to use protein-polymer hybrids in cell therapies, e.g. to help heart attack patients recover by regenerating healthy heart tissue. The advantage of the waterless protein-polymer compounds is that they prolong the survival of the patient and support the implantation of the transplanted cells.

Original publication:

Diffusive-like motions in a solvent free protein-polymer hybrid.

Giorgio Schirò, Yann Fichou, Alex P. S. Brogan, Richard Sessions, Wiebke Lohstroh, Michaela Zamponi, Gerald J. Schneider, François-Xavier Gallat, Alessandro Paciaroni, Douglas J. Tobias, Adam Perriman, Martin Weik; Phys. Rev. Lett. Vol. 126, No. 8(2021) DOI 10.1103/PhysRevLett.126.088102

More information:

The research also involved scientists from the following institutions:

University of Bristol, UK, School of Biochemistry, Bristol, UK, King's College London, UK, Louisiana State University, USA, University of California, USA, Università degli Studi di Perugia, Italy.

Press release issued by Forschungszentrums Jülich on 2 August 2012 „Maschinen des Lebens arbeiten auch ohne Wasser“ (in German)