Sugars and proteins, united for better or worse

The incorrect addition of sugary groups to various proteins in the human body has been linked to various diseases for more than 70 years, such as cancer, Alzheimer's and tumor calcinosis. The first step to develop treatments and vaccines against them is to know how these protein-sugar interactions occur at the molecular level. The Institute of Biocomputing and Physics of Complex Systems of the University of Zaragoza leads international research with this objective.

Although it may seem to us that they are things that always go separately, the presence of carbohydrates (sugar groups) in proteins is essential for numerous functions of the human body and is directly related to various diseases. These sugars act as 'tags' on the surface of proteins and regulate functions as important as communication and cell division. If they are not added correctly, uncontrolled cell growth can occur, as occurs in cancer metastasis. They have also been linked to degenerative processes such as Alzheimer's, tumor calcinosis and deregulation of lipid metabolism, among others.

The project led by Ramón Hurtado Guerrero, Araid researcher at the Institute of Biocomputing and Physics of Complex Systems (BIFI) of the University of Zaragoza, is framed in this context. In collaboration with universities and national and international centers, his group studies how the union occurs between sugars and various proteins that recognize carbohydrates, and seeks to explain the mechanisms behind the associated diseases.

To obtain this information, X-ray crystallography and electron cryomicroscopy are mainly used, along with other biophysical techniques. Thanks to these structural techniques, the structures of proteins or complexes formed by them and sugars are obtained.

The final objective of the project is "to understand the molecular bases that underlie the interaction of proteins that recognize carbohydrates and their 'target' sugars," explains Hurtado-Guerrero, "to reveal their reaction and recognition mechanisms, and to be able to design selective inhibitors that modulate its activity in various diseases, as well as vaccines and selective treatments".

What is the crystallography of proteins?
Protein crystallography is a biophysical technique in which, under certain conditions of medium and temperature, crystals of a specific protein are obtained. For this to happen, the protein molecules must have been arranged periodically and repetitively within the crystal. When X-rays are incident on the crystals (normally generated by a particle accelerator or synchrotron, in our case Diamond in Oxford or Alba in Barcelona), the molecules structured in the crystals deflect these rays following a pattern that depends on the arrangement of its atoms and molecules. These patterns are collected and processed mathematically until obtaining a kind of 'map' of the interior of the protein that allows, finally, to draw the position of each of its atoms, as if it were an atomic-scale photograph. Today it is still the technique with the highest resolution at a structural level, and one of the means that provides the most information about the internal structure of molecules and compounds.