Competitive intra- and extracellular nutrient sensing by the transporter homologue Ssy1p.
Recent studies of Saccharomyces cerevisiae revealed sensors that detect extracellular amino acids (Ssy1p) or glucose (Snf3p and Rgt2p) and are evolutionarily related to the transporters of these nutrients. An intriguing question is whether the evolutionary transformation of transporters into nontransporting sensors reflects a homeostatic capability of transporter-like sensors that could not be easily attained by other types of sensors. We previously found SSY1 mutants with an increased basal level of signaling and increased apparent affinity to sensed extracellular amino acids. On this basis, we propose and test a general model for transporter- like sensors in which occupation of a single, central ligand binding site increases the activation energy needed for the conformational shift between an outward-facing, signaling conformation and an inward-facing, nonsignaling conformation. As predicted, intracellular leucine accumulation competitively inhibits sensing of extracellular amino acids. Thus, a single sensor allows the cell to respond to changes in nutrient availability through detection of the relative concentrations of intra- and extracellular ligand.
Wu
Boqian
B
Carlsberg Laboratory, DK-2500 Copenhagen, Denmark.
Ottow
Kim
K
Poulsen
Peter
P
Gaber
Richard F
RF
Albers
Eva
E
Kielland-Brandt
Morten C
MC
D015079:2-Isopropylmalate Synthase / Q000378:metabolism; D000465:Algorithms; D047908:Intracellular Signaling Peptides and Proteins; D007930:Leucine / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D010649:Phenylalanine / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D017459:Receptors, Amino Acid / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D017459:Receptors, Amino Acid; C120527:SSY1 protein, S cerevisiae; C074632:STP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D010649:Phenylalanine; D015079:2-Isopropylmalate Synthase; C080062:LEU4 protein, S cerevisiae; D007930:Leucine