Crystallization chaperones

We generate nanobodies that facilitate the crystallization of challenging targets and identifies nanobodies that stabilize unique conformations to study the structure, function and dynamics of these proteins.

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Structural enzymology

We are interested in understanding how enzymes function at the molecular and atomic level. We combine structural biology with protein engineering and enzyme kinetics to study how structure determines function. 

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Protein-protein interactions

Protein-protein complexes play an important role in biology and disease. In order to characterise these "transient" protein-protein interactions, we are developping Nanobody-based methods to stabilize PPIs.
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Transient protein-protein interactions

Protein–protein interactions (PPIs) are central to most biological processes - from intercellular communication to programmed cell death - and therefore represent a large and important class of targets for human therapeutics. A crucial step towards understanding these biological processes and targeting them for therapy is mapping networks of physical DNA-, RNA- and protein-protein interactions, the “interactome network”, of an organism of interest as completely and accurately as possible. Recently a large number of biological pathway and network databases have been developed to capture the expanding knowledge of protein-protein interactions. However, the complete understanding of molecular interactions requires high resolution 3D structures as they provide key atomic details about binding interfaces and information about structural changes that accompany protein-protein interactions. 

 

Recently, we identified nanobodies that stabilize the ß2AR-Gs complex. One of these nanobodies (red) that inhibits the GTP driven dissociation of  ß2AR-Gs was used to obtain the high-resolution crystal structure of this complex, providing the first view of transmembrane signaling by a GPCR  (Rasmussen et al. 2011a). Currently, we are developping generic methods to produce Nanobodies that stabilize (transient) protein-protein interactions in a ternary complex. More stable ternary complexes can be purified, characterized and their structure can be solved by X-ray crystallography. Building on our first successes, we envision to extend the power of nanobody-aided crystallography to stretch ahead of monomeric proteins, reaching transient protein-protein interactions and maybe transient protein-nucleic acid interactions.