Title: | Agonist-specific conformational changes in the yeast alpha-factor pheromone receptor |
Address: | "Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, 01655-0122, USA" |
ISSN/ISBN: | 0270-7306 (Print) 1098-5549 (Electronic) 0270-7306 (Linking) |
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" |
Keywords: | "Amino Acid Sequence Fungal Proteins/agonists/*chemistry/physiology GTP-Binding Proteins/metabolism Ligands Mating Factor Molecular Sequence Data Peptides/physiology Protein Binding *Protein Conformation Receptors, Mating Factor Receptors, Peptide/agonists;" |
Notes: | "MedlineBukusoglu, G Jenness, D D eng GM34719/GM/NIGMS NIH HHS/ Research Support, U.S. Gov't, P.H.S. 1996/09/01 Mol Cell Biol. 1996 Sep; 16(9):4818-23. doi: 10.1128/MCB.16.9.4818" |