个人简介

B.S., Yale University, 1974; Ph.D., Harvard University, 1980. Professor, Caltech, 1989-2004; Dickinson Professor, 2004-. Investigator,1997-2002; 2005-; Full Investigator, 2002-05. Executive Officer for Chemistry, 2002-06; Executive Officer, 2007-.

研究领域

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.

Biochemistry and Molecular Biophysics; Chemistry

近期论文

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Yang, J. G. and Rees, D. C. "The Allosteric Regulatory Mechanism of the E. coli MetNI Methionine ABC Transporter" J. Biol. Chem. [epub ahead of print] (2015). Zhang, L., Morrison, C. N., Kaiser, J. T., and Rees, D. C. “Nitrogenase MoFe-protein from Clostridium pasteurianum at 1.08 Å Resolution: Comparison to the Azotobacter vinelandii MoFe-protein” Acta Cryst. D71, 274-282 (2015). Tezcan, F. A., Kaiser, J. T., Howard, J. B., and Rees, D. C. "Structural Evidence for Asymmetrical Nucleotide Interactions in Nitrogenase" J. Amer. Chem. Soc.137, 146-149 (2014). Kamajaya, A., Kaiser, J. T., Lee, J., Reid, M., and Rees, D. C. “The Structure of a Conserved Piezo Channel Domain Reveals a Topologically Distinct beta Sandwich Fold” Structure 22, 1520-1527 (2014). Wang, K. Sitsel, O, Meloni, G., Autzen, H. E., Andersson, M., Klymchuk, T., Nielsen, A. M., Rees, D. C., Nissen, P., and Gourdon, P. “Structure and Mechanism of Zn2+-transporting P-type ATPases” Nature 514, 518-522 (2014). Spatzal, T., Perez, K., Einsle, O., Howard, J. B. and Rees, D. C. “Ligand Binding to the FeMo-cofactor: Structures of CO-bound and Reactivated Nitrogenase” Science 345, 1620-1623 (2014). PMC4205161 Walton, T. A., Idigo, C. A., Herrera, N., and Rees, D. C. “MscL: Channeling Membrane Tension” Pflugers Arch - Eur J Physiol 467, 15-25 (2015). Lee, J. Y, Yang, J. G., Zhitnitsky, D., Lewinson, O. and Rees, D. C. "Structural Basis for Heavy Metal Detoxification by an Atm1-type ABC Exporter" Science 343, 1133-1136 (2014). Yang, K. Y., Haynes, C. A., Spatzal, T., Rees, D. C., and Howard, J. B. “Turnover-Dependent Inactivation of the Nitrogenase MoFe-Protein at High pH” Biochemistry 53, 333-343 (2014). PMC3932303 Basta, T., Wu, H.-J., Morphew, M. K., Lee, J., Ghosh, N., Lai, J, Heumann, J. M., Wang, K., Lee, Y. C., Rees, D. C., and Stowell, M. H. B. “Self-Assembled Lipid and Membrane Protein Polyhedral Nanoparticles” Proc. Natl. Acad. Sci. USA 111, 670-674 (2014). PMC3896197 Meloni, G., Zhang, L., and Rees, D.C. “A transmembrane Type-2-like Cu2+ site in the P1B-3-type ATPase CopB: implications for metal selectivit.” ACS Chem. Biol. 9, 116-121 (2014). PMC3947036 Zhang, L., Kaiser, J. T, Meloni, G., Yang, K.Y., Spatzal T., Andrade, S. L., Einsle, O., Howard, J. B., and Rees, D. C. “The Sixteenth Iron in the Nitrogenase MoFe Protein” Angew. Chem. Int. Ed. Engl. 52, 10529-10532 (2013). PMC2891402 Walton, T. A. and Rees, D. C. “Structure and Stability of the C-terminal Helical Bundle of the E. coli Mechanosensitive Channel of Large Conduc-tance” Protein Science 22, 1592-1601 (2013). PMC3831674 Howard, J. B., Kechris, K. J., Rees, D. C., and Glazer, A. N. “Multiple Amino Acid Sequence Alignment of Nitrogenase Component 1: Insights into Phylogenetics and Structure-Function Relationships”PLOS One 8, 1-12 (2013). PMC3760896 Pieper, U., Schlessinger, A., Kloppmann, E., Chang, G. A., Chou, J.J., Dumont, M. E., Fox, B. G., Fromme, P., Hendrickson, W. A., Malkowski, M. G., Rees, D. C., Stokes, D. L., Stowell, M. H., Wiener, M. C., Rost, B., Stroud, R. M. Stevens, R. C., and Sali, A. “Coordinating the Impact of Structural Genomics on the Human a-Helical Transmembrane Proteome” Nat. Struct. Mol. Biol. 20, 135-138, (2013). PMC3645303 Lai, J.Y., Poon, Y.S., Kaiser, J T. and Rees, D.C. "Open and Shut: Crystal Structures of the Dodecylmaltoside Solubilized Mechanosensitive Channel of Small Conductanse from E. coli and H. pylori at 4.4 Å and 4.1 Å Resolution" Protein Science 22, 502-209 (2013). PMC3610056 Johnson, E., Nguyen, P.T., Yeates, T.O., and Rees, D. C. “Inward Facing Conformations of the MetNI Methionine ABC Transporters: Implications for the Mechanism of Transinhibition” Protein Science 21, 84-96 (2012). PMC3323782 Bobyr, E., Lassila, J.K., Wiersma-Koch, H.I., Fenn, T.D., Lee, J.J., Nikolic-Hughes, I., Hodgson, K.O., Rees, D.C., Hedman, B. and Herschlag, D. "High-resolution Analysis of Zn2+ Coordination in the Alkaline Phosphatase Superfamily by EXAFS and X-ray Crystallography” J. Mol. Biol. 415, 102-117 (2012). PMC3249517 Tirado-Lee, L., Lee, A., Rees, D.C. and Pinkett, H.W. "Classification of a Haemophilus influenzae ABC Transporter HI1470/71 Through Its Cognate Molybdate Periplasmic Binding Protein, MolA" Structure 19, 1701-1710 (2011). PMC3258573 Spatzal, T., Aksoyoglu, M., Zhang, L., Andrade, S.L.A., Schleicher, E., Weber, S., Rees, D.C. and Einsle, O. "Evidence for Interstitial Carbon in Nitrogenase FeMo Cofactor" Science 334, 940 (2011).PMC3268367