Andrzej Krezel

Structural NMR studies of proteins and protein-protein interactions

The three-dimensional structures of proteins are essential for explaining biological functions, effects of mutations, and serve as models for designing new active forms of drugs. Advances in molecular biology techniques allow rapid detection of the specific interactions between proteins and other biomolecules. However, even the structures of two proteins, known to interact with each other, are not sufficient to define their respective binding sites. Few structures of protein-protein and protein-nucleic acid complexes have been solved by NMR techniques. Theoretical models of these complexes are often built from high resolution structures of the components. The least defined parts of such models are the molecular interfaces. These regions are also the most biologically interesting and promising sites from a pharmaceutical point of view.

Our research is focused on structural studies of the specificity of protein-protein and protein-nucleic acid interactions. We use multi-dimensional heteronuclear solution NMR spectroscopy as a primary experimental technique. NMR techniques are unique in providing details of conformation as well as molecular dynamics of proteins in solution in free and bound forms. We are using extracellular domains of TGF-b receptors and TGF-b as model systems for studying protein-protein interactions.

Lab Homepage