James H. Hurley, Ph.D.
LMB
STRUCTURAL BIOLOGY & CELL SIGNALING SECTION
NIDDK, National Institutes of Health
Building 50
, Room 4517
50 South Dr.
Bethesda, MD 20814
Tel: 301-402-4703
Fax: 301-480-0639
Email: james.hurley@nih.gov
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Research Website:
http://www-mslmb.niddk.nih.gov/hurley/
Education / Previous Training and Experience:
B.A., San Francisco State University, 1984
M.S., San Francisco State University, 1986
Ph.D., University of California, San Francisco, 1990
Research Statement:
The interplay between proteins and membrane lipids is central to almost every aspect of cell biology. This laboratory is interested in fundamental questions of how the interactions between proteins and membranes determine cell and organelle shape and the evolution of shape over time, how protein-membrane interactions turn on and off the signals that control essential cell processes, and how pathogens such as HIV-1 subvert and co-opt these interactions.
The roots of our research program are in the power of x-ray crystallography to reveal the structures of membrane-interacting proteins at high resolution, leading to insights in the physical basis of protein-membrane interactions. Crystallography continues to be at the heart of our research because of its unequaled power to reveal the shape of proteins and the atomic basis for protein-protein and protein-lipid interactions. The reconstitution of membrane remodeling pathways in synthetic membrane systems has recently taken on equal importance in the lab. Both the crystallographic and membrane reconstitution programs in the lab are driven by our ability to generate intact, biochemically functional multiprotein complexes using expression systems that include E. coli, yeast, insect cells, and mammalian cell culture. Membrane remodeling is reconstituted in the lab in giant unilamellar vesicles, a method that allows visualization of membrane structural changes by fluorescence microscopy. These core approaches are complemented by lower resolution studies in solution or on membranes by hydrodynamic, small angle x-ray scattering, and site-specific fluorescent labeling approaches within the lab, and through collaborative electron microscopy. The presence of the membrane has a profound effect on the nature of protein-protein interactions, and a variety of fluorescence-based approaches are being pursued to study these interactions in their native membranous environment. Biological hypotheses generated from structural and in vitro analyses are tested in vivo whenever possible. In our lab we use yeast as a model system, and function in human cells is tested in collaboration with other laboratories in the outstanding cell biology and virology communities at NIH.
Selected Publications:
Wollert, T., Wunder, C., Lippincott-Schwartz, J. and Hurley, J. H. Membrane Scission by the ESCRT-III Complex. Nature
458, 172-177 (2009).
Yang, D., Rismanchi, N., Renvoise, B., Lippincott-Schwartz, J., Blackstone, C. and Hurley. J. H. Structural Basis for Midbody Targeting of Spastin by the ESCRT-III Protein CHMP1B. Nat. Struct. Mol. Biol
15, 1278-1286 (2008).
Lee, H., Elia, N., Ghirlando, R., Lippincott-Schwartz, J. and Hurley. J. H. Midbody Targeting of the ESCRT Machinery by a Non-Canonical Coiled-Coil in CEP55. Science 322, 576-580 (2008).
Lee, S., Joshi, A., Nagashima, K., Freed, E. O. and Hurley, J. H. Structural Basis for Viral Late Domain Binding to Alix. Nat. Struct. Mol. Biol. 14, 194-199 (2007).
Kostelansky, M. S., Schluter, C., Tam, Y. Y. C., Lee, S., Ghirlando, R., Beach, B. M., Conibear, E. and Hurley, J. H. Molecular Architecture and Functional Model of the Complete Yeast ESCRT-I Heterotetramer. Cell 129, 485-498 (2007).
Hierro, A., Rojas, A. L., Rojas, R., Murthy, N., Effantin, G., Kajava, A. V., Steven, A. C., Bonifacino, J. S. and Hurley, J. H. Functional Architecture of the Retromer Cargo-Recognition Complex. Nature 449, 1063-1067 (2007).
Lee, S., Tsai, Y. C., Mattera, R., Smith, W. J., Kostelansky, M. S., Weissman, A. M., Bonifacino, J. S. and Hurley, J. H. Structural Basis for Ubiquitin Recognition and Autoubiquitination by the A20 Zinc Finger and Inverted UIM of Rabex-5. Nat. Struct. Mol. Biol. 13, 264-271 (2006).
Im, Y. J., Raychaudhuri, S., Prinz, W. A. and Hurley, J. H. Structural Mechanism for Sterol Sensing and Transport by OSBP-Related Proteins. Nature 437, 154-158 (2005).
Canagarajah, B., Coluccio Leskow, F., Ho. Y.S.J., Mischak, H., Saidi, L., Kazanietz, M.G. and Hurley, J. H. Structural Mechanism for Lipid Activation of the Rac-specific GAP, b2-Chimaerin. Cell 119, 407-418 (2004).
Prag, G., Misra, S., Jones, E. A., Ghirlando, R., Davies, B. A., Horazdovsky, B. F. and Hurley, J. H. Mechanism of Monoubiquitin Recognition by the CUE Domain of Vps9p. Cell 113, 609-620 (2003).
Misra, S., Puertollano, R., Kato, Y., Bonifacino, J. S., and Hurley, J. H. Structural Basis for Acidic-Cluster-Dileucine Sorting Signal Recognition by VHS Domains. Nature 415, 933-937 (2002).
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