Peter Unwin, PhD

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.