Document Detail


Hyper- and hyporesponsive mutant forms of the Saccharomyces cerevisiae Ssy1 amino acid sensor.
MedLine Citation:
PMID:  18307103     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Saccharomyces cerevisiae integral membrane protein Ssy1p functions with Ssy5p and Ptr3p to sense extracellular amino acids. Signal transduction leads to processing and nuclear localization of Stp1p and Stp2p, transcriptional activators of many amino acid transporter genes. Ssy1p is structurally related to amino acid permeases, but unable to transport amino acids. We isolated SSY1 mutants that constitutively activate a target promoter. Dose-response analysis showed that the mutants are hyperresponsive, requiring less inducer to give strong signaling than does the wild type. Another mutant (Ssy1p(T639I)) turned out to be hyporesponsive, i.e., it signals only at high inducer concentration. In accordance with a transporter-like mechanism for Ssy1p function we suggest that the hyper- and hyporesponsive mutant forms differ from the wild-type sensor by being more and less inclined, respectively, to adopt an outward-facing, signaling conformation. Coordinate conformational dynamics of the sensor complex was supported by additive effects of combinations of constitutive SSY1, PTR3 and SSY5 alleles. Assuming structural similarity of Ssy1p to the distantly related bacterial leucine transporter LeuT(Aa), several activating substitutions were located near the substrate binding site while others were on the periphery of Ssy1p. We suggest analyses of transporter-like sensors as an approach to understand key features of transporters.
Authors:
Peter Poulsen; Richard F Gaber; Morten C Kielland-Brandt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular membrane biology     Volume:  25     ISSN:  0968-7688     ISO Abbreviation:  Mol. Membr. Biol.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-29     Completed Date:  2008-09-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9430797     Medline TA:  Mol Membr Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  164-76     Citation Subset:  IM    
Affiliation:
Carlsberg Laboratory, Copenhagen Valby, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Alleles
Amino Acid Sequence
Amino Acid Substitution
Amino Acid Transport Systems, Neutral / genetics
Amino Acids / metabolism*
Gene Expression Regulation, Fungal
Intracellular Signaling Peptides and Proteins
Membrane Proteins / metabolism*
Models, Biological
Molecular Sequence Data
Mutant Proteins / isolation & purification,  metabolism*
Mutation / genetics
Nuclear Proteins / metabolism
Promoter Regions, Genetic / genetics
Protein Binding
Protein Processing, Post-Translational
Protein Structure, Secondary
RNA-Binding Proteins / metabolism
Saccharomyces cerevisiae / chemistry,  genetics,  metabolism*
Saccharomyces cerevisiae Proteins / genetics,  metabolism*
Sequence Analysis, DNA
Signal Transduction
Transcription Factors / metabolism
Chemical
Reg. No./Substance:
0/AGP1 protein, S cerevisiae; 0/Amino Acid Transport Systems, Neutral; 0/Amino Acids; 0/Intracellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/Mutant Proteins; 0/Nuclear Proteins; 0/RNA-Binding Proteins; 0/SSY1 protein, S cerevisiae; 0/STP1 protein, S cerevisiae; 0/Saccharomyces cerevisiae Proteins; 0/Transcription Factors

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