Structural Biology

X-ray crystallography has played a pivotal role in all projects. In the GPCR projects, it has allowed to describe the interaction with ligands (agonists and antagonists) with the receptor, as well as the induced conformational changes. In projects with DARPins, it has clarified the binding epitope, and thereby elucidated the mode of action of pharmacologically active DARPins. In projects involving Armadillo Repeat Proteins, it has been part of the protein design cycle, to verify the molecular structure to exact details, and the binding mode of the ligand, to influence the next design cycle.

Conversely, protein engineering has also helped crystallography in general: Using rigidly fused DARPins as new crystallization chaperones, several structures could be determined that did not give rise to diffracting crystals otherwise.

Cryo-Electron microscopy of surface receptors is being used, both as single particles and in whole cell tomography, in collaboration with the group of Ohad Medalia. Here, the capability of creating tailor made binding proteins is playing a key role. NMR is used in several collaborations, involving all of the main research directions.