Week 3 Regulation and Sensing Flashcards
Major Modes of Regulation
- No control: normal GE
- Transcriptional: Gene on/off –> no mRNA
- Translational:
> Enzyme activity controlled: translation proceeds but no product
> **Product activity controlled: no protein made
Transcriptional Control: DNA-Binding Proteins
- Homodimers (highly sequence specific): recognition by DNA structure (NOT sequence-reading), esp by operator region of the promoter
- Regulator proteins can act at level of single genes, operons or regulons
Transcriptional Negative Control (repression and induction)
- Repression (Anabolic): Sufficient products stop transcription (repressor binds when product not needed)
- Induction (Catabolic): Degrades products if already sufficient (repressor binds when degradation is not needed)
Transcriptional Positive Control (Activators)
- Promote RNAP and DNA promoter binding
> Activator binds to inducer molecule –> activate transcription
> Either via activator binding site or directly with RNAP
> Ex. Maltotriose (Trisac) is the inducer that informs the cell of Maltose (disac) presence
Post-Transcriptional Control: Antisense RNAs
Small “non-coding” that binds mRNA complements –> degradation before translation
> Fe-limitation: prevents translation of Fe-utilizing genes when Fe is low
> Rare in prokaryotes
Post-Transcriptional Control: Riboswitches
mRNA self-regulation:
> Regulatory parts of mRNA that binds metabolites
> Influences secondary structures of mRNA to prevent translation
> Rare in prokaryotes
Sensing and Signal Transduction
- IC: inducers, co-repressors or effectors
- EC: GE and signals
> Ex. Temp/pH: lipid modification
> Ex. Light/O2: motility, photosynthesis
> Cell concentration: virulence, bioluminescence
Two-Component Regulatory Systems
- Sensor kinase:
> Bind signals, autophosphorylates, and phodsphorylate response regulator - Response regulator:
> Activated by phosphorylation –> DNA binding and transcriptional control of genes in response to environment
> Activators or repressors
> Rare in Archaea; absent in obligate IC pathogens
Examples:
Stimulus –> input –> transmitter –> receiver –> output –> response
EnvZ/OmpR Osmoregulation System
- EnvZ - sensor kinase that detects periplasmic pressure
- OmpR - response regulator that binds to DNA to regulate transcription
- OmpC - small pore OM porin protein with higher electrostatic potential
- OmpF - large pore OM porin protein with reduced electrostatic potential
> Hyperosmotic shock: EnvZ phosphorylated –> OmpF repressed and OmpC activated
Hypoosmotic shock: EnvZ unphosphorylated –> OmpF activated and OmpC repressed
Quorem Sensing (density-dependent)
Certain cell reponses are wasted if low in number/strength
> Pathogens: toxin
> Bioluminescent bacteria (Lux gene: AHL –> LuxR –> Lux operon –> LuxI (AHL synthase)
> Biofilm formation: exopolysac production
Autoinducers (species-specific signaling)
Binds to activators/repressors to regulate GE; GE self-regulation via positive feedback
> Acyl Homoserine Lactones (AHLs)
> Cyclic furans (A1-2)
> Quinolines and small peptides
ex. Virulence factors, exopolysac, biofilms
Chemotaxis
- Response to chemical signals
> Stimulus/Transducers (MCPs): methyl-accepting Chemotaxis Proteins (Tar MCP of E.Coli senses aspartate and maltose (attractants) and cobalt/nickel (repellants)
> CheA as sensor kinase (repellants increase CheA kinase activities)
> CheY as response regulator (governs flagellar rotation direction) - Control flagellar rotation
> CheY phosphorylation state (P=CW/tumble; interact with Fli); unphosphorylated (CCW) **Repellant increases CheY phosphorylation –> tumble
> CheZ dephosphorylates –> favors run/titer tumbles - Adaptation: detect [metabolite] over time
> CheR (methylase; mimics binding att/repel) and CheB (RR; de-methylase; accept P groups) modify MCPs
> CheA (SS; phosphorylates CheB)
> Repellants favor de-P MCP (CheB active) –> run
> Attractants favor P MCP (CheB inactive) –> tumble
