Proteins

InBioS-Proteins Structure-Function research teams aim at obtaining a more integrated view of protein function within the context of living organisms. Proteins, being the main products of genetic information, are the pivotal biological macromolecules that determine the structure and function of all living cell systems. Five major lines of research are pursued and involve all the available and related technologies in molecular and cellular biology, bacteriology, biochemistry, biophysics, bioinformatics, protein and membrane chemistry, enzymology, structural biology and protein modelisation. The research is strongly supported by the two CIP platforms Protein Factory and Robotein.

1. Protein Folding. Understanding the basic aspects of protein folding is crucial in describing virtually all biological processes, ranging from transcription to molecular motors and diseases associated with misfolded proteins. The underlying mechanisms for protein misfolding and amyloid fibril formation are investigated using several protein models.

2. Protein engineering research is dedicated on improving existing proteins and enzymes to make them more effective with higher affinity, longer lasting effects and/or greater selectivity. Hybrid proteins as the results of two different joined protein sequence are studied in order to interact with different ligands (polysaccharides, RNA ,...)

3. Protein-ligand interactions. Proteins interact with ligands of various sizes that can be substrates, inhibitors, metals, effectors, nucleic acids, lipid bilayers or other proteins. Undesired alterations of these interactions can transform a normal cellular process into an aberrant one, resulting in many types of pathologies.

4. Protein supramolecular assemblies and protein networks. Proteins do not act as isolated entities. In a cellular context, they are strongly affected by permanent and transient interactions with other biomolecules. Their expression and activity is intensively regulated through connections in protein networks. The analysis of the interactions and the structural changes of the Escherichia coli divisome proteins are studied in order to have a dynamic picture of the cell division process.

5. Bacterial resistance topic deals with proteins involved in the peptidoglycan biosynthesis in earlier steps (C55-PP phosphatases) or in last steps (transglycosylases and transpeptidases). A major bacterial resistance problem concerns resistance to β-lactam antibiotics via the emergence of modified targets (resistant PBPs) and synthesis of β-lactam destroying enzymes (β-lactamases). Those proteins are targets in the search of “drug lead compound” via new approaches (new molecular scaffold, screening of small compounds libraries, fragment based screening via X-ray crystallography).