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Mol Genet Genomics

Title:		Effects of mutations in the N terminal region of the yeast G protein alpha-subunit Gpa1p on signaling by pheromone receptors
Author(s):		Roginskaya M; Connelly SM; Kim KS; Patel D; Dumont ME;
Address:		"Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, PO Box 712, Rochester, NY 14642, USA"
Journal Title:		Mol Genet Genomics
Year:		2004
Volume:		20040207
Issue:		2
Page Number:		237 - 248
DOI:		10.1007/s00438-004-0975-y
ISSN/ISBN:		1617-4615 (Print) 1617-4623 (Linking)
Abstract:		"The sites and modes of interaction between G protein-coupled receptors and their cognate heterotrimeric G proteins remain poorly defined. The C-terminus of the Galpha subunit is the best established site of contact of G proteins with receptors, but structural analyses and crosslinking studies suggest the possibility of interactions at the N-terminus of Galpha as well. We screened for mutations in the N-terminal region of the Galpha subunit encoded by the yeast GPA1 gene that specifically affect the ability of the G protein to be activated by the yeast alpha-mating factor receptor. The screen led to identification of substitutions of glutamine or proline for Leu18 of Gpa1p that reduce the response to the pheromones alpha-factor and a-factor without affecting cellular levels of the subunit or its ability to interact with beta and gamma subunits. The mutations do not appear to affect the intrinsic ability of the G protein to be converted to the activated state. The low yield of different mutations with this phenotype indicates either that the N-terminal segment of the yeast Galpha subunit does not undergo extensive interactions with the alpha-factor receptor, or that this region can not be altered without detrimental effects upon the formation of G protein trimers"
Keywords:		"Alleles Fluorescence Fungal Proteins/metabolism GTP-Binding Protein alpha Subunits/*genetics GTP-Binding Protein alpha Subunits, Gq-G11 Immunoblotting Membrane Proteins Mutagenesis Mutation, Missense/*genetics *Phenotype Plasmids/genetics Receptors, Phero;"
Notes:		"MedlineRoginskaya, M Connelly, S M Kim, K S Patel, D Dumont, M E eng GM59357/GM/NIGMS NIH HHS/ Comparative Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Germany 2004/02/10 Mol Genet Genomics. 2004 Mar; 271(2):237-48. doi: 10.1007/s00438-004-0975-y. Epub 2004 Feb 7"