Senyon Choe
e-mail: choe@salk.edu
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Our research goals deal with problems related to protein assembly and molecular recognition in biology. Two main themes of research relate to understanding mechanisms of molecular working of "Potassium channels" and "transmembrane signaling receptors of TGF-beta family".
For K channel studies, we would like to combine structural analyses of K channel domains by x-ray crystallography and by NMR methods with functional analyses of isolated domains in solution and in the membrane. The goal is to better understand the mechanisms of ion selectivity and conductance, gating, and modulation of channels through protein-protein interaction.
Our study on the structure of the complex of cytokines and their transmembrane receptors is to understand the mechanism of transmembrane signaling by TGF-beta family. Our previous work on the first crystal view into the extracellular domain of the type II serine kinase receptor family (this one for activin) demostrated a conserved neurotoxin fold for this entire family of receptors. More recently, we have studied protein complexes formed between the cell surface domains of receptors and antagonist proteins in complex with protein ligands. We hope to characterize the formation of a heterohexameric assembly between ligands and receptors at molecular level so that we can couple such molecular assembly events to biological signaling outputs. On a computational front, our long-term interest is to develop a methodology to obtain energetic profiles of two or more interacting molecules for structure-guided drug design and also for quantitative analyses of properties of associatingmolecules. HIV Integrase is one such target system and also for HIV drug development.
Kreusch, A., Pfaffinger, P., Stevens,
C.F., Choe, S. (1998). Crystal structure of the tetramerization
domain of the Shaker potassium channel. Nature 392: 945-8.
Robinson, R., Turbedsky, K., Kaiser,
D., Marchand, J.-B., Higgs, H.N., Choe, S., Pollard, T. (2001) Crystal
structure of Arp2/3 Complex. Science, 294, 1679-1684.
Choe, S. (2002) Potassium Channel Structures, Nature Reviews Neuroscience, 3, 115-121.
Roosild, T., Miller, S., Booth, I., Choe, S. (2002) A Mechanism of regulating Transmembrane Potassium Flux by a Ligand-mediated Switch. Cell, 109, 781-791.
Groppe, J., Greenwald, J., Wiater, E., Rodriguez-Leon, J., Economides, A., Kwiatkowski, W., Affolter, M., Vale, W., Izpisua Belmonte, J.C., Choe, S. (2002) Structural Basis of BMP signaling inhibition by Noggin, Nature 420, 636-42.
Greenwald, J., Groppe, J., Gray, P., Wiater, E., Kwiatkowski, W., Vale, W., Choe, S. (2003) The BMP7/ActRII extracellular domain complex provides new insights into the cooperative nature of receptor assembly. Molecular Cell, 11, 605-17.
Senyon Choe received his Ph.D. from the University of California, Berkeley. He has been a faculty member in the Structural Biology Laboratory at The Salk Institute since 1993.
