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Nicotinic Acetylcholine Receptors
Electrical and chemical signaling in the nervous system is controlled in part by actions of a class of molecules called nicotinic acetylcholine receptors. The receptor receives and processes natural chemical signals carried by the neurotransmitter, acetylcholine. Receipt and processing of these signals are critical to muscle control and movement, automatic control of bodily organs to maintain survival, and brain functions such as mood, thinking, and many forms of sensory perception. Defects in or loss of acetylcholine signaling seems to be involved in a number of neuropsychiatric and other disorders, as would be expected given the wide variety of important roles of the receptor in normal brain and body function. The nicotinic acetylcholine receptors also are the body’s primary targets of nicotine from tobacco products.
Electron microscopy has yielded an overall model but there remains a lack
of information about the structure at atomic scale resolution. The receptor
has approximately five-fold symmetry and roughly forms a cylinder with a channel
10-20Å in diameter (schematic figure from Stryer, Biochemistry). The
transport of ions through the channel is determined by the presence of several
negatively charged amino acids in the center of the channel that prevent the
transport of anions and limit the transport of cations by size exclusion.
In collaboration with Dr. R. Lukas of the Barrow Neurological Institute, we have begun a project to determine these structures. Small crystals of the receptor have been obtained and work in underway to obtain larger crystals suitable for X-ray diffraction studies. The goal is to determine the three dimensional structure in order to advance our understanding of the function and design drugs that interact with the receptor for therapeutic usage.
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Photosynthesis Center Arizona State University Box 871604 Room PSD 209 Tempe, AZ 85287-1604
13 February 2006 |
phone: (480) 965-1963 fax: (480) 965-2747 |