The general interest of our lab is to understand mechanisms for regulation of signaling proteins through intra- and inter-molecular interactions. Specificity, we focus on receptor-mediated signaling pathways involved in neuron development and axonal guidance, such as the semaphoring/plexin and the NGF/Trk receptor tyrosine kinase pathways, including the receptors themselves and downstream targets and regulatory proteins. We use a combination of biochemical, X-ray crystallographic and cell biological approaches to seek an understanding of the regulatory mechanisms at the atomic level.
A better understanding of the regulatory mechanisms for players in these complicated signaling systems will not only have implications on how cells respond properly to various inputs through precisely controlled protein machineries in general, but also help develop new therapies for related diseases such as neurodegenerative disorder and cancer.
RESEARCH INTERESTS
Signal transduction
Structural biology
RECENT PUBLICATIONS
He, H., Yang, T. Terman, J.R., Zhang, X., "Crystal structure of the plexin A3 intracellular region reveals an autoinhibited conformation through active site sequestration" Proc Natl Acad Sci USA, 100:2586-2591, 2009
Jura, N. Endres, N. F. Engel, K. Deindl, S. Das, R. Lamers, M. H. Wemmer, D. E. Zhang, X. Kuriyan, J., "Mechanism for activation of the EGF receptor catalytic domain by the juxtamembrane segment" Cell, 137:1293-1307, 2009
Zhang, X., Pickin K. P., Bose R., Jura N., Cole, P. A., and Kuriyan, J., "Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interface." Nature, 450:741-744, November 2007
Zhang, X., Gureasko, J., Shen, K., Cole, P. A., and Kuriyan, J., "An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor." Cell, 125:1137-1149, 2006
SIGNIFICANT PUBLICATIONS
He, H., Yang, T. Terman, J.R., Zhang, X., "Crystal structure of the plexin A3 intracellular region reveals an autoinhibited conformation through active site sequestration" Proc Natl Acad Sci USA, In press 2009
Zhang, X., Pickin K. P., Bose R., Jura N., Cole, P. A., and Kuriyan, J., "Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interface." Nature, 450:741-744, 2007
Zhang, X., Gureasko, J., Shen, K., Cole, P. A., and Kuriyan, J., "An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor" Cell, 125:1137-1149, 2006
Schwartz, J. C.*, Zhang, X.*, Fedorov, A. A., Nathenson, S. G., and Almo, S. C. (*equal contributions), "Structural basis for co-stimulation by the human CTLA-4/B7-2 complex" Nature, 410:604-608, 2001
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