Date post: | 15-Jan-2016 |
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Sites of regulation
Feedback inhibition
Mechanism of allosteric inhibition
Repression and Induction
Mechanism of repression- Negative control
Mechanism of repression-control by co-repressor
Operon= a cluster of genes under controlof a single promoterRegulon?
Arginine synthesis
Mechanism of induction
Lac operon
Mechanism of induction-negative control
Positive vs. Negative control
• Repressors are “negative control”– An active repressor (- inducer or + corepressor)
stops transcription
• Activator proteins are “positive control”– The regulatory protein (activator) promotes
transcription– Example: maltose regulon
Activator protein without inducer-positive control
Activator protein with inducer
DNA binding proteins
• Non-specific, eg. histones– Small proteins, high + charge
• Specific– Frequently dimers– Interact with inverted repeats– Eg. lac repressor
DNA binding proteinsDimeric proteins (e.g., lac repressor) interact with
inverted repeats
Attenuation• Positive and negative control affect initiation of
transcription• Attenuation affects continuation of transcription
– Eg. the tryptophan operon has a leader that includes two tryptophan residues
– When tryptophan is lacking, the translation is delayed
– The speed of translation determines which of two mRNA double-stranded loops form
• One of the two possible loops is a termination signal
How does it work?
• Transcription and translation occurring almost simultaneously– Rate of transcription influenced by rate of
translation
• Translation of leader PEPTIDE regulates transcription– Synthesis of leader terminates transcription,
and leader synthesis is inhibited by low Trp
Attenuation: leader sequence
Attenuation: delayed translation
Ribosome pauses at trp codon, stem loop that forms DOES not terminate transcription
Attenuation: undelayed translation
Leader peptide is formedStop codon or stem-loop structure can form in mRNAAnd transcription is attentuated
Global control: catabolite repression- a variety of unrelated genes
regulated
Diauxic growth
Catabolite repression
• Catabolite activator protein (CAP) assists binding of RNA polymerase to promoter
• CAP can bind only when it first binds cAMP• Adenylate cyclase: ATP -> cAMP +
pyrophosphate• Glucose inhibits adenylate cyclase and stimulates
cAMP excretion• Catabolite repression is similar to positive control,
but the difference is the global nature of catabolite repression
CAP binding site on the lac operon
Quorum sensing
• Also a form of global control• Relatively recent discovery• AHL-acylated homoserine lactone
– Diffusible
– Inducer needs activator protein
• Example, bioluminescence and luxR activator– Only when [AHL ] is high enough will LuxR activate
the lux operon
2 component regulatory systems
• Maltose=effector, BUT if signal not DIRECTLY involved, but needs to be transmitted and changed = signal transduction
• Sensor protein=– kinase, phosphorylates compounds,
– membrane associated
• Phosphoryl group transmitted to another regulator IN the cell– Often a DNA binding protein involved in transcription
• Many examples, N-fixation, sporulation,chemotaxis
2 component regulatory systems
Chemotaxis• Attractants decrease rate of autophosphorylation• Repellant increased autophosphorylation• CheA-CheW=transducer• CheY controls switch
– cheY-P tumbles, CCW-CW
• CheB phosporylated by CheA-P, but slower response than CheY-P
• CheB involved methylation– Fully methylated = best for repellants– cheB-P demethylates, occurs when attractants High– Degree of methylation regulates attraction/repulsion
Chemotaxis