Proteins function by forming complexes with other biomolecules. Some of these are tight and well-defined, others are weak and dynamic. We study the biophysical nature of complexes of proteins with other proteins and ligands.
The formation of complexes is essential for the function of most proteins. Enzymes bind substrates and allosteric ligands and many other proteins bind to DNA, RNA, lipids, polysaccharides or other proteins. We have studied many transient complexes formed by electron transfer (ET) proteins. The biological function requires fast turn-over of such complexes. Many ET complexes are on the border of specific and non-specific.
Our research has demonstrated the important role of dynamics in complex formation. The encounter complex, a dynamic state in which the proteins sample each other’s surface, is an essential element of the process. Also ligand binding to proteins can involve dynamics. Protein structure is not rigid, but rather breathes over many timescales. Such mobility is often vital for protein function.
We study the relation between structure, dynamics and function of protein-ligand complexes. We produce most proteins and protein variants in house and characterize the complexes using various biophysical methods, most importantly with paramagnetic NMR spectroscopy. We develop specific paramagnetic tags for this purpose that are attached via two arms to the protein, to yield a rigid, well-defined tag with strong paramagnetic effects.