Structural Mechanisms of Protein Assemblies

Fundamental processes in biology such as genetic recombination and DNA replication require the coordinated activity of a number of proteins because these processes involve multiple steps of molecular recognition and chemistry. In the past 6 years, I have become particularly intrigued by the possibility of using NMR spectroscopy to investigate the dynamic nature of multi-protein complexes and the transitions that need to occur for forward progression of protein assemblies. Such studies are specifically designed to take advantage of the unique capabilities of NMR to complement the snapshots of multi-protein assemblies that can be obtained by other structural methods, such as X-ray crystallography and cryo electron microscopy. I particularly appreciate this multi-pronged structural approach not only because it is essential to tackling complex problems, but also because I greatly enjoy working in collaborative projects. The bulk of our efforts in this area is in the study of DNA replication, recombination and repair assemblies. In the past 3 years, interest in protein ubiquitination assemblies has also begun to arise, initially based on the discovery of S100 proteins binding to components of E3 ubiquitin ligase complexes briefly described above. This interest has been further stimulated by our recent studies of protein ubiquitination in the yeast spliceosome.

• Signal Transduction by EF-hand Calcium-Binding Proteins
  • The structural basis for selectivity in intracellular Ca²⁺ signal transduction
  • Intracellular and extracellular signal transduction mediated by S100 proteins
• Structural Mechanisms of Protein Assemblies
  • Structural mechansims for progression of DNA processing assemblies
  • Structural, biochemical and functional studies of ubiquitination signaling