W2: Signal Transduction in Prok: TCS- Taxis and Motility

• two component systems (TCS) convert external signals into a phosphorelay
• component 1 -> sensor protein (usually kinase) which auto phosphorylates then transfers the phosphate onto component 2, very specific for given stimulus signal

  component 2 -> response regulator, receives signal and elicits response (like TF)
• more TCS in bacterial strains means that they are adaptable to many environments
• organization of prototypical TCS in bacteria

  • extracellular signal binds sensor kinase -> conformation change turns kinase on -> kinase auto phosphorylates on HISTIDINE residue -> phosphate transfers from kinase to response regulator on ASPARTIC ACID residue -> response, generally digital response

  
• TCS are usually organized in a more expanded/regulated way where proteins transfer phosphates onto the next protein until it reaches the response regulator, this is analog signalling since there are more outcomes available

  
• a TCS always has a HISTIDINE kinase transferring a phosphate to a response regulator with an ASPARTIC ACID residue, if there are more than 2 components the phosphate always transfers from histidine to aspartic acid back and forth

  
• phosphorelay of multiple transfers can involve 1 protein with multiple domains OR multiple proteins
• regulatory mechanisms of TCS

  • response regulator (RR)
  • phosphorylation of connected HK
  • dephosphorylation by specific phosphatases
  • stimulation of intrinsic autophosphatase activity
  • histidine kinase (HK)
  • autokinase activity can be stimulated/repressed by specific stimulus
  • RR phosphatase activity of HK can be modulated
  • inhibition of phosphotransfer
  • inhibition of dimerization domains
  • regulation of the expression of the two component protein
• the structure of TCS are:

  • signal sensor with kinase domain (histidine residue)
  • response regulator (aspartic acid residue)

  
• an example of a TCS is sporulation

  • 5 HK (ABCDE) which have receptors for different signals but have the same histidine kinase domain to phosphorylate the same RR (Spo0F, internal receiver) which transfers its phosphate to Spo0B (histidine phosphotransferase) and then Spo0A (final RR, becomes TF)
  • RapA and Spo0E are phosphatases to serve as regulation on the pathway

  
• TCS often display positive OR negative feedback loops
• phosphorylated RR have an affect on a cellular processes which can be transcriptional or post translational
• types of stimuli that bacteria can respond to are light (phototaxis), nutrients (chemotaxis), and oxygen (aerotaxis)

  
• 1 response that bacteria have to external stimuli is movement (taxis)

  
• methylation acts as a negative feedback loop to control swimming motility for better sampling of environment