Title
Agonist-specific conformational changes in the yeast alpha-factor pheromone receptor
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Molecular Genetics and Microbiology
Publication Date
1996-09-01
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
The yeast alpha-factor pheromone receptor is a member of the G-protein-coupled receptor family. Limited trypsin digestion of yeast membranes was used to investigate ligand-induced conformational changes in this receptor. The agonist, alpha-factor, accelerated cleavage in the third intracellular loop, whereas the antagonist, desTrp1,Ala3-alpha-factor, reduced the cleavage rate. Thus, the enhanced accessibility of the third intracellular loop is specific to the agonist. alpha-Factor inhibited cleavage weakly at a second site near the cytoplasmic terminus of the seventh transmembrane helix, whereas the antagonist showed a stronger inhibition of cleavage at this site and at another site in the C-terminal domain of the receptor. The alpha-factor-induced conformational changes appeared to be inherent properties of the receptor, as they were retained in G-protein-deficient mutants. Moreover, a mutant receptor (ste2-L236H) that affects the third loop and is defective for G-protein coupling retained the ability to undergo the agonist-induced conformational changes. These results are consistent with a model in which G-protein activation is limited by the availability of specific contacts between the G protein and the third intracellular loop of the receptor. The antagonist appears to promote a distinct conformational state that differs from either the unoccupied or the agonist-occupied state.
DOI of Published Version
10.1128/MCB.16.9.4818
Source
Mol Cell Biol. 1996 Sep;16(9):4818-23.
Journal/Book/Conference Title
Molecular and cellular biology
Related Resources
PubMed ID
8756640
Repository Citation
Bukusoglu G, Jenness DD. (1996). Agonist-specific conformational changes in the yeast alpha-factor pheromone receptor. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1128/MCB.16.9.4818. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/151