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Scripps Research Joint Appointments

Center for Integrative Molecular Biosciences

Research Focus

Nicotinic Acetylcholine Receptor and Fast Synaptic Transmission

The nicotinic acetylcholine (ACh) receptor is the neurotransmitter-gated ion channel involved in rapid transmission of electrical signals across the nerve-muscle synapse. Our goal is to understand how this channel works, using electron microscopy to determine its structure trapped in different functional states. We investigate tubular crystals, derived from Torpedo electric organ, in which the ACh receptors, lipids and the receptor-clustering protein rapsyn are organized almost as they are in vivo. We have shown that when acetylcholine enters the binding pockets it triggers a concerted conformational change which opens the membrane-spanning pore by destabilizing a gate in the middle of the membrane. The nature of this conformational change is now being explored at near-atomic resolution.

Education

Ph.D., Cell Biology, University of Cambridge, 1968

Awards & Professional Activities

Fellow of the Royal Society of London (1983-)
Rosenstiel Award for Basic Medical Research (1991)
Louis-Jeantet Prize for Medicine (1996)
Gregori Aminoff Prize in Crystallography (1999)
Royal Society Croonian Lecturer and Medal (2000)

Selected References

Unwin, N. and Fujiyoshi Y. (2012) Gating movement of acetylcholine receptor caught by plunge-freezing. J. Mol. Biol. 422:617-34.

O'Brien, J. and Unwin, N.  (2006)  Organization of spines on the dendrites of Purkinje cells.  Proc. Natl. Acad. Sci. 103:1575-1580.

Unwin, N.  (2005)  Refined structure of the nicotinic acetylcholine receptor at 4Å resolution.  J. Mol. Biol. 346:967.989.

Miyazawa, A., Fujiyoshi, Y. and Unwin, N.  (2003)  Structure and gating mechanism of the acetylcholine receptor pore.  Nature 423:949-955.