Document Detail


Interaction between transmembrane domains five and six of the alpha -factor receptor.
MedLine Citation:
PMID:  10846179     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The alpha-factor pheromone receptor (STE2) activates a G protein signal pathway that induces conjugation of the yeast Saccharomyces cerevisiae. Previous studies implicated the third intracellular loop of this receptor in G protein activation. Therefore, the roles of transmembrane domains five and six (TMD5 and -6) that bracket the third intracellular loop were analyzed by scanning mutagenesis in which each residue was substituted with cysteine. Out of 42 mutants examined, four constitutive mutants and two strong loss-of-function mutants were identified. Double mutants combining Cys substitutions in TMD5 and TMD6 gave a broader range of phenotypes. Interestingly, a V223C mutation in TMD5 caused constitutive activity when combined with the L247C, L248C, or S251C mutations in TMD6. Also, the L226C mutation in TMD5 caused constitutive activity when combined with either the M250C or S251C mutations in TMD6. The residues affected by these mutations are predicted to fall on one side of their respective helices, suggesting that they may interact. In support of this, cysteines substituted at position 223 in TMD5 and position 247 in TMD6 formed a disulfide bond, providing the first direct evidence of an interaction between these transmembrane domains in the alpha-factor receptor. Altogether, these results identify an important region of interaction between conserved hydrophobic regions at the base of TMD5 and TMD6 that is required for the proper regulation of receptor signaling.
Authors:
P Dube; A DeCostanzo; J B Konopka
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  275     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2000 Aug 
Date Detail:
Created Date:  2000-09-25     Completed Date:  2000-09-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  26492-9     Citation Subset:  IM    
Affiliation:
Program in Molecular and Cellular Biology and the Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook, New York 11794-5222, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Amino Acid Substitution
Cysteine
Membranes
Molecular Sequence Data
Mutagenesis, Site-Directed
Phenotype
Protein Structure, Secondary
Receptors, Mating Factor
Receptors, Peptide / chemistry*,  genetics
Structure-Activity Relationship
Transcription Factors / chemistry*,  genetics
Yeasts
Grant Support
ID/Acronym/Agency:
GM55107/GM/NIGMS NIH HHS; T32CAO9176/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Mating Factor; 0/Receptors, Peptide; 0/Transcription Factors; 52-90-4/Cysteine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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