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NEWS
June 2022 ESRFnews
Data taken at the ESRF and elsewhere have uncovered the structural changes involved in the breathing of proteins. The results could affect protein design and structure prediction, as well as the understanding of the causes of disease.
In the 1970s, studies using nuclear magnetic resonance (NMR) showed that aromatic amino acids in proteins are able to flip 180 degrees, despite often being located in a protein s tightly packed core. Scientists speculated that large scale breathing motions must be necessary to accommodate the flips, but the structural details of such motion have remained a mystery.
Now, researchers from the Institut de Biologie Structurale on the EPN campus and the Institute for Advanced Biosciences, also in Grenoble, have used state-of-the-art macromolecular crystallography beamlines at the ESRF ID30A-1, ID30B, ID23-1 and ID23-2 and at Diamond Light Source in the UK to help map the structural changes. Together with NMR experiments, the work reveals how, in specific steps, a protein is able to generate a void around an aromatic ring to allow its flipping to take place (Nature 602 695).
According to the researchers, the discovery has implications for both protein design and structure prediction, by highlighting how even small changes in the delicate balance of interactions stabilising the core can lead to major changes in the protein structure . The fact that big effects can derive from small causes also helps to show, they believe, how novel biological functions can be acquired during evolution, for instance in the gain or loss of hydrogen bonds. Moreover, they say, the ability to see what is happening in the core of the structures of moving proteins [provides] insights into how very small alterations can be the cause of many diseases.
Protein breathing leads to big structural changes
Fruit fly sees in high-def 3D The human eye has a single large lens and a retina densely packed with photoreceptors, which gives us high- definition vision. By contrast, insect eyes consist of thousands of tiny and apparently simple units, which capture only a pixelated, low-resolution view of the world. That has been the prevailing view until now. Mikko Juusola at Sheffield
University in the UK, along with colleagues at the University of Oulu in Finland, the University of Lund in Sweden and the University of Szeged in Hungary, came to the ESRF beamline ID16B to take high-contrast, ultra high-speed nanoscale in vivo images of the eyes of the fruit fly, Drosophila melanogaster. Together with
data taken at DESY in Germany, the researchers discovered that the insect s photoreceptors twitch in a highly organised manner, mirror-symmetric between left and right compound eyes. As the fly travels, the resultant images combine into one that is not coarsely pixelated, but continuous and in high-definition 3D (PNAS 119 e2109717119). These results change radically
the current understanding of how insect compound eyes work, says Juusola. The ESRF contribution was critical, as it gave us the first global evidence, including the high- resolution, high-speed dynamics of how photoreceptors contract photomechanically to light changes.
Head of a male fruit fly (Drosophila melanogaster) showing one of its compound eyes (red).
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