The objectives of the research application are to understand the structural features of the nicotinic acetylcholine receptor (AChR) and to relate these structures to the function of the receptor. The structure of the acetylcholine binding sites will be investigated by photoaffinity labelling to determine respective contributions of the subunits to the binding sites. Photoaffinity labels derivatized from d- tubocurarine, ethidium bromide and conotoxins will be designed to probe the contributions gamma- and delta-subunits to the agonist binding sites. The topology of the AChR primary subunit sequence will be analyzed by labelling of protein exposed on the extracellular surface of the AChR. The labelled sites will be identified by isolation of labelled fragments and identification of labelled residues. The location of putative intracellularly exposed fragment a156-179 will specifically be evaluated. Chemical crosslinking will be used to define near-neighbor relationships of the subunits and of individual amino acids within subunits.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Modified Research Career Development Award (K04)
Project #
1K04NS001618-01
Application #
3075215
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1992-12-01
Project End
1997-11-30
Budget Start
1992-12-01
Budget End
1993-11-30
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030