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Department of Neuroscience

Peter Unwin, PhD

Professor Emeritus
Department of Neuroscience
California Campus
Laboratory Website
(858) 784-9109

Research Focus

Nicotinic Acetylcholine Receptor and Fast Synaptic Transmission

The nicotinic acetylcholine receptor is the transmitter-gated ion channel at the nerve-muscle synapse. It has been fine-tuned through evolution to transduce a chemical signal into an electrical signal with maximum efficiency and speed. 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 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.

Awards & Professional Activities

Fellow of the Royal Society of London (1983-)
Fellow of Trinity College, Cambridge (1987-)
Rosenstiel Award for Basic Medical Research (1991)
Louis-Jeantet Prize for Medicine (1996)
Fellow of the Academy of Medical Sciences, London (1998-)
Gregori Aminoff Prize in Crystallography (1999)
Royal Society Croonian Lecturer and Medal (2000)

Selected References

Unwin, N. (2013) Nicotinc acetylcholine receptor and the structural basis of neuromuscular transmission: insights from Torpedo postsynaptic membranes. Quart. Rev. Biophys. 46:283-322.

Zuber, B. and Unwin, N. (2013) The structure and superorganisation of acetylcholine receptor-rapsyn complexes. Proc. Natl. Acad. Sci. USA 110:10622-10627.

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. USA 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.