Douglas C. (Doug) Rees
Roscoe Gilkey Dickinson Professor of Chemistry; Investigator, Howard Hughes Medical Institute; Executive Officer for Biochemistry and Molecular Biophysics
Research InterestsProtein Structure and Energetics; X-ray Crystallography
Assistant: Phoebe Ray
The research interests of the Rees group emphasize the general area of structural bioenergetics, using crystallographic and functional approaches to characterize water-soluble and membrane proteins participating in various energy transduction pathways.
Studies of metalloproteins containing complex cofactors with either molybdenum or tungsten have defined the unusual structures of the FeMo-cofactor of nitrogenase and the more widespread Mo-cofactor that participate in basic reactions of the biological nitrogen and sulfur cycles.
Studies of integral membrane proteins have emphasized energy transduction processes associated with photosynthetic and respiratory processes, mechanosensation, and of ABC transporter systems that mediate nutrient uptake into bacteria.
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.