By rigidifying flexible regions and obscuring aggregative surfaces, Nanobody complexes warrant conformationally uniform samples that are key to protein structure determination by X-ray crystallography. The elucidation of the first GPCR structure in its active state using conformationally selective Nanobodies demonstrates the power of the Xaperone platform to speed up and reduce the cost of generating diffracting quality crystals of challenging targets.

Xaperones are antigen binding fragments from heavy chain only antibodies that: 

The coming years we want to deploy the potential of our nanobody platform for the structural and functional investigation of proteins that are not conductive to conventional methods. Such targets include amyloidogenic proteins and membrane proteins (especially GPCRs).

Redox Regulation

 

The Redox regulation team, under the guidance of Joris Messens, specializes in the in vitro reconstitution of thiol/disulfide electron transfer pathways and the study of the kinetics during electron transfer. One of the key aims is to better understand how the recurring thioredoxin motive catalyses so many diverse reactions, from the reduction of oxidized arsenate reductase up to the formation and/or exchange of disulfide bonds during the oxidative protein folding process. Currently, the focus is on three diverse thiol/disulfide exchange systems: (i) thioredoxin, (ii) oxidoreductases and their role in protein folding and (iii) arsenate reductases. In the long term, we will exploit our biochemical, structural and quantum chemical expertise in thiol/redox-chemistry through three projects: “Co-translational protein folding at the ribosomes”, “New drugs for the treatment of Mycobacterium tuberculosis with a clear focus on the unexplored mycothiol/mycoredoxin redox pathway”, and “Oxidative stress signal transduction in plants”.

For more details, visit the Brussels Center for Redox Biology website at http://redox.vub.ac.be.

The RNA modification team, under the supervision of Wim Versées, specializes in the elucidation of the structure-function relationship of nucleoside and nucleic acid-modifying enzymes, using a combination of physicochemical techniques and protein engineering approaches. For years we have been studying the mechanism of protozoal nucleoside hydrolyses. Currently we have shifted the focus to the elucidation of the mechanism and 3-dimensional structure of tRNA-modifying enzymes and enzyme complexes, of both prokaryotic and eukaryotic origin. We are therefore concentrating particularly on enzymes involved in modification of the wobble position. These post-transcriptional tRNA modifications play a primordial role in the translation process, as they influence cognate codon recognition, stabilization of the codon-anticodon wobble base pairing, and correct aminoacylation. Our main goal is to characterize the interactions between the proteins in the enzyme complexes, their interaction with the RNA substrates, the chemistry of the reaction, and the regulation by external factors. Finally, these studies should contribute to a better understanding of the mechanisms underlying diseases caused by tRNA undermodification, which result in (mitochondrial or cytoplasmic) translation infidelities.

For more details, contact Wim Versées.