A Dual-Sensing Receptor Confers Robust Cellular Homeostasis.
Cells have evolved diverse mechanisms that maintain intracellular homeostasis in fluctuating environments. In bacteria, control is often exerted by bifunctional receptors acting as both kinase and phosphatase to regulate gene expression, a design known to provide robustness against noise. Yet how such antagonistic enzymatic activities are balanced as a function of environmental change remains poorly understood. We find that the bifunctional receptor that regulates K(+) uptake in Escherichia coli is a dual sensor, which modulates its autokinase and phosphatase activities in response to both extracellular and intracellular K(+) concentration. Using mathematical modeling, we show that dual sensing is a superior strategy for ensuring homeostasis when both the supply of and demand for a limiting resource fluctuate. By engineering standards, this molecular control system displays a strikingly high degree of functional integration, providing a reference for the vast numbers of receptors for which the sensing strategy remains elusive.
Center for Integrated Protein Science Munich (CiPSM), Ludwig-Maximilians-Universität München, Großhaderner Straße 2-4, 82152 Martinsried, Germany; Department of Biology I, Microbiology, Ludwig-Maximilians-Universität München, Großhaderner Straße 2-4, 82152 Martinsried, Germany.
Hannah
H
Schramke
Physik Department, Technische Universität München, James Franck Straße 1, 85747 Garching, Germany.
Filipe
F
Tostevin
Department of Biology I, Microbiology, Ludwig-Maximilians-Universität München, Großhaderner Straße 2-4, 82152 Martinsried, Germany.
Ralf
R
Heermann
Physik Department, Technische Universität München, James Franck Straße 1, 85747 Garching, Germany. Electronic address: gerland@tum.de.
Ulrich
U
Gerland
Center for Integrated Protein Science Munich (CiPSM), Ludwig-Maximilians-Universität München, Großhaderner Straße 2-4, 82152 Martinsried, Germany; Department of Biology I, Microbiology, Ludwig-Maximilians-Universität München, Großhaderner Straße 2-4, 82152 Martinsried, Germany. Electronic address: jung@lmu.de.
Kirsten
K
Jung
D000595:Amino Acid Sequence; D004926:Escherichia coli / Q000166:cytology* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D006706:Homeostasis; D008954:Models, Biological; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D019897:Periplasm / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D013312:Stress, Physiological; D013696:Temperature
D029968:Escherichia coli Proteins; D050505:Mutant Proteins; C489580:KdpD protein, E coli; D011494:Protein Kinases; D010744:Phosphoric Monoester Hydrolases; D011188:Potassium