Soluble homologs of the nicotinic receptor

Institution:	University of California, San Diego
Investigator(s):	Scott Hansen, BS, MS
Award Cycle:	2003 (Cycle 12)	Grant #: 12DT-0013	Award: $52,858
Subject Area:	Nicotine Dependence
Award Type:	Dissertation Awards

Abstracts

Initial Award Abstract

Receptors are crucial proteins or machinery that help a nerve fire in the brain or muscle. Specifically, a receptor seizes a signal released from a previous nerve and then fires the nerve or tissue upon which the receptor is found thus propagating a nerve impulse. One such receptor is the nicotinic acetylcholine receptor. Its name derives from two chemicals known to be bound by the receptor thus activating it. The first, acetylcholine, is naturally occurring and constantly present. The second, nicotine, is not natural and enters the body though tobacco use. Nicotine finds its way to the nicotinic acetylcholine receptor binds and fires the receptor. This unnatural event is brought under control but in the process leads to addiction. In order to understand addiction it would be helpful to understand the details of nicotine binding. Unfortunately receptors are so small that we can not simply visualize them by conventional methods. More sensitive methods require that the protein dissolve in pure water. The nicotinic acetylcholine receptors from humans do not dissolve in water. However, recently a soluble nicotinic acetylcholine receptor was found in a fresh water snail. We have produced a second soluble receptor from a salt water snail. Using these two proteins I hope to elucidate the intimate details of nicotine binding to receptor. Furthermore these proteins provide a map where by the human receptors may be made soluble. Successful characterization of these types of protein will greatly enhance our knowledge of the effects of tobacco use.

Publications

Structural and ligand recognition characteristics of an acetylcholine-binding protrotein from aplysia californica.
Periodical: Journal of Biological Chemistry			Index Medicus:
Authors: Hansen SB, Talley TT, Radic Z, Taylor P				ART
Yr: 2004	Vol: 279	Nbr: 23	Abs:	Pg: 24197-24202

Contemporary paradigms for cholinergic ligand design guided by biological structure.
Periodical: Bioorganic Medical Chemistry			Index Medicus:
Authors: Taylor P, Hansen SB, Talley TT, Hibbs RE, Radic Z				ART
Yr: 2004	Vol: 14	Nbr: 8	Abs:	Pg: 1875-1877

Structures of aplysia AChBP complexes with nicotinic agonists and antagonists reveal distinctive binding interfaces and conformations.
Periodical: Embo Journal			Index Medicus:
Authors: Hansen SB, Sulzenbacher G, Huxford T, Marchot P, Taylor P, et al				ART
Yr: 2005	Vol:	Nbr:	Abs:	Pg:

Crystal structure of a Cbx-AChBP complex reveals essential interactions between snake alpha-neurotoxins and nicotinic receptors.
Periodical: Embo Journal			Index Medicus:
Authors: Bourne Y, Talley TT, Hansen SB, Taylor P, Marchot P				ART
Yr: 2005	Vol: 24	Nbr: 8	Abs:	Pg: 1512 - 1522

Structural and ligand recognition characteristics of an acetylcholine-binding protrotein from aplysia californica.
Periodical: Journal of Biological Chemistry			Index Medicus:
Authors: Hansen SB, Talley TT, Radic Z, Taylor P				ART
Yr: 2004	Vol: 279	Nbr: 23	Abs:	Pg: 24197-24202

Contemporary paradigms for cholinergic ligand design guided by biological structure.
Periodical: Bioorganic Medical Chemistry			Index Medicus:
Authors: Taylor P, Hansen SB, Talley TT, Hibbs RE, Radic Z				ART
Yr: 2004	Vol: 14	Nbr: 8	Abs:	Pg: 1875-1877

Structures of aplysia AChBP complexes with nicotinic agonists and antagonists reveal distinctive binding interfaces and conformations.
Periodical: Embo Journal			Index Medicus:
Authors: Hansen SB, Sulzenbacher G, Huxford T, Marchot P, Taylor P, et al				ART
Yr: 2005	Vol:	Nbr:	Abs:	Pg:

Crystal structure of a Cbx-AChBP complex reveals essential interactions between snake alpha-neurotoxins and nicotinic receptors.
Periodical: Embo Journal			Index Medicus:
Authors: Bourne Y, Talley TT, Hansen SB, Taylor P, Marchot P				ART
Yr: 2005	Vol: 24	Nbr: 8	Abs:	Pg: 1512 - 1522