Doug Rees to give the 2010 Fritz Lipmann Lectureship
Douglas C. Rees, a Howard Hughes Medical Institute investigator and professor of Chemistry at the California Institute of Technology, will give the Fritz Lipmann Lectureship at the 2010 ASBMB Annual meeting. This lectureship, which is awarded every two years, recognizes investigators who make conceptual advances in biochemistry, bioenergetics, and molecular biology.
Rees has been an HHMI investigator since 1997 and is the Roscoe Gilkey Dickinson professor of Chemistry at the California Institute of Technology as well as an adjunct professor of Physiology at the University of California, Los Angeles, School of Medicine. He received his B.S. degree in Molecular Biophysics and Biochemistry from Yale University in 1974 and his Ph.D. in Biophysics from Harvard University in 1980, working with William Lipscomb. From 1980 to 1981, he was a postdoctoral fellow at Harvard and from 1981 to 1982, he was a postdoctoral fellow at the University of Minnesota with James Howard. He then joined the faculty at the University of California, Los Angeles before moving to Caltech in 1989.
Rees has made pivotal contributions to understanding the structure of integral membrane proteins, membrane transport mechanisms, and metalloenzyme structure and mechanism. His research focuses on structural bioenergetics, which is the description of biological energy transduction processes at a molecular level. One of his group’s major goals is to characterize the structures and mechanisms of ATP-dependent transduction systems, including membrane proteins that catalyze energy transduction processes associated with transport, mechanosensation, and respiration-linked electron transfer reactions.
Rees’ graduate training was in x-ray crystallography, and while studying as a postdoctoral fellow at Minnesota, he became interested in how ATP and other large molecules are used for energy in the body. One way in which organisms harness this energy is via ATP binding cassette (ABC) transporters, which use the binding and hydrolysis of ATP to pump molecules against concentration gradients across cell membranes. When Rees started as an independent investigator, no structure of an ABC transporter had been determined. Rees surveyed several ABC transporters from a variety of organisms before deciding that BtuCD, the protein that imports vitamin B12 into Escherichia coli, would be appropriate for his structural studies. Rees and his colleagues were able to produce crystals of the transporter and solve its structure. Based on their results, they proposed a model for the transporter’s molecule pumping ability. This initial structure also enabled them to crystallize and solve the structure of the intact, nucleotide-free HI1470/1 transporter from Haemophilus influenza, a member of the family of binding protein-dependent bacterial ABC transporters that mediate the uptake of metal-chelate species, including heme and vitamin B12.
Since solving these structures, Rees has added many other projects to his repertoire, including:
Nitrogenase: The biological conversion of dinitrogen to ammonia is catalyzed by the nitrogenase enzyme system, which consists of two component proteins, the iron (Fe-) protein and the molybdenum-iron (MoFe-) protein. Rees and his colleagues have determined the three-dimensional structures of both proteins and associated metal centers and are currently developing mechanistic models for the nitrogenase reaction.
Extremely Thermostable Metalloproteins: The structures of the tungsten-containing aldehyde ferredoxin oxidoreductase and a rubredoxin from Pyrococcus furiosus, an archaeon that grows optimally at 100° C, have been determined by Rees. He is now using these structures to help identify the origins of the proteins’ extreme thermostability.
Membrane Proteins: Structural and sequence analyses of membrane proteins indicate that the same general structural and energetic considerations govern the three-dimensional structures of both water-soluble and membrane proteins. Currently, Rees and his colleagues are looking at the structures of succinate quinone oxidoreductase and photosynthetic reaction centers to assess the generality of this conclusion and to establish the structural organization of the redox centers.
Fibroblast Growth Factors (FGF): These proteins stimulate the growth and development of many different cell types. Rees has solved the structures of two members of the FGF family and recently determined how the anti-ulcer drug, sucrose octasulfate, and heparin fragments bind to FGF. He is currently probing the structures of nucleic acid complexes, transcriptional regulators, and a variety of other electron transfer proteins.
Rees is a member of the American Academy of Arts and Sciences and the National Academy of Sciences and is the 2008 Dorothy Crowfoot Hodgkin awardee of the Protein Society. He has an extensive record of community service, including a stint on the Science Advisory Board and as chair of NIH’s Biophysical Chemistry study section, and is currently the editor of Annual Reviews of Biophysics and Biomolecular Structure.