It is proposed to determine the general topography of the nicotinic acetylcholine receptor with respect to the postsynaptic membrane. The regions of each of the four subunits that are exposed to the external and internal aqueous environments of the membrane will be identified by chemical modification and enzymatic degradation followed by separation of the modified proteins and identification by amino acid sequencing. Similarly the parts of the receptor subunits that interact with the lipid bilayer will be identified by chemical modification within the bilayer followed by isolation of the modified regions and sequencing of the amino acids involved. Such studies will be correlated with the known structure (at the primary level) of the receptor. It is also proposed to identify the parts of the receptor that constitute the ion-channel through which cations flow in response to acetylcholine binding and in addition to localize all the binding sites for acetylcholine. These studies should serve as models for membrane proteins, membrane channels and for understanding the complexity and variability of multiple interactions between receptors and drugs that effect their physiological activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS010294-17
Application #
3394210
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1988-01-01
Project End
1991-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
17
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Arts and Sciences
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Bertazzon, A; Conti-Tronconi, B M; Raftery, M A (1992) Scanning tunneling microscopy imaging of Torpedo acetylcholine receptor. Proc Natl Acad Sci U S A 89:9632-6