Split Histidine Kinases Enable Ultrasensitivity and Bistability in Two-Component Signaling Networks

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Amin, Munia ; Porter, Steven L. ; Soyer, Orkun S. (2013)
  • Publisher: Public Library of Science
  • Journal: PLoS Computational Biology (issn: 1553-734X, vol: 9)
  • Related identifiers: doi: 10.1371/journal.pcbi.1002949, doi: 10.1371/journal.pcbi.1002949, pmc: PMC3591291
  • Subject: Computational Biology | Systems Biology | Applied Mathematics | Research Article | Biology | Mathematics | Biochemical Simulations | Microbiology | Signaling Networks | Evolutionary Processes | Prokaryotic Models | Theoretical Biology | Bacteriology | Bacterial Biochemistry | QD | Evolutionary Biology | Model Organisms | QH301 | Microbial Physiology | Bacterial Evolution | Nonlinear Dynamics

Bacteria sense and respond to their environment through signaling cascades generally referred to as two-component signaling networks. These networks comprise histidine kinases and their cognate response regulators. Histidine kinases have a number of biochemical activities: ATP binding, autophosphorylation, the ability to act as a phosphodonor for their response regulators, and in many cases the ability to catalyze the hydrolytic dephosphorylation of their response regulator. Here, we explore the functional role of “split kinases” where the ATP binding and phosphotransfer activities of a conventional histidine kinase are split onto two distinct proteins that form a complex. We find that this unusual configuration can enable ultrasensitivity and bistability in the signal-response relationship of the resulting system. These dynamics are displayed under a wide parameter range but only when specific biochemical requirements are met. We experimentally show that one of these requirements, namely segregation of the phosphatase activity predominantly onto the free form of one of the proteins making up the split kinase, is met in Rhodobacter sphaeroides. These findings indicate split kinases as a bacterial alternative for enabling ultrasensitivity and bistability in signaling networks. Genomic analyses reveal that up 1.7% of all identified histidine kinases have the potential to be split and bifunctional.
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