Douglas C. (Doug) Rees

Assistant: Ann Mao

The research interests of the Rees group have centered on the structures and mechanisms of complex metalloproteins and integral membrane proteins, particularly those involved in ATP-dependent transduction processes. The metalloprotein work defined the unusual structures of the nitrogenase FeMo-cofactor and the more widespread Mo-cofactor that participate in basic reactions of the biological nitrogen and sulfur cycles, while the membrane protein studies have addressed the structural basis of photosynthesis, mechanosensation and transport processes.  The current work on membrane proteins emphasizes bacterial ATP Binding Cassette (ABC) transporters mediating nutrient translocation, while the metalloprotein efforts focus on defining the molecular mechanism of nitrogenase in biological nitrogen fixation.

Metalloproteins Our work on metalloproteins has centered on proteins that incorporate unusual molybdenum and tungsten containing centers, including the FeMo-cofactor of nitrogenase and the more widespread molybdenum cofactor that participate in many of the basic reactions of the biological nitrogen and sulfur cycles. We have determined structures for the nitrogenase FeMo-cofactor and the pterin containing molybdenum-cofactor, which defined the structural biology of molybdenum and tungsten, the only second and third row transition metals to be utilized biologically. From a structural bioenergetics perspective, nitrogenase is also of interest as a structurally characterized energy transduction system that couples nucleotide hydrolysis to redox chemistry, and exhibits striking parallels to nucleotide-dependent signal transduction systems.

Membrane Proteins We are particularly interested in transporters and channels that exist in multiple conformational states that are sensitive to the binding of ligands, changes in membrane potential or the application of mechanical forces. Our long-term goal is to structurally define selected transporters and channels in distinct functional states to understand how the conformations of membrane proteins are coupled to the cellular environment. Systems of current interest include ATP Binding Cassette (ABC) transporters that utilize the binding and hydrolysis of ATP to translocate ligands across the membrane, and prokaryotic mechanosensitive channels (Msc), including those of large (MscL) and small (MscS) conductance that couple channel gating with membrane tension. We are also interested in exploring the general parallels between ABC transporters and nitrogenase in terms of the coupling between nucleotide state and the formation of distinct complexes that are crucial for mediating unidirectional translocation of ligands (nutrients and electrons, respectively). In addition to their functional implications, structural studies of membrane proteins are of general interest to address the consequences of folding in a predominantly nonaqueous environment.