Engineering of Membrane Proteins

Pluecki3

One of the biggest challenges in the study of the structure and biophysics of membrane proteins is that these proteins are extremely difficult to handle: They are hard to produce in large amounts, they are very unstable and they often denature when solubilized.

We strongly believe that this problem can be solved by two strategies: by engineering of the membrane protein itself and by designing stabilizing binding proteins.

We are therefore developing novel evolutionary strategies to stabilize such proteins as G-protein-coupled receptors, which are the targets of about half of all pharmaceuticals in use today. Via this approach we are trying to make them amenable to structural studies to learn the fundamentals of membrane protein architecture and ideally to be able to study many members of this very important family. Using novel approaches of selection, mutagenesis and screening, the sequence of these proteins is being explored to unravel the principles of stability and folding.

We also developed strategies to select binding proteins (e.g. Designed Ankyrin Repeat Proteins or antibody fragments) against the native state of integral membrane proteins and use such proteins to support stabilization and crystallization.