Lac Operon

Table of Contents• Transcriptional Regulation in prokaryotes– Types of Regulation– Types of genes: Based on the small effector molecule

• Operon– Definition and Discovery

• Lac operon– Components of the Lac Region– Lac metabolism in Escherichia coli

• Regulation of Lac Operon– Negative Control– Positive Control

Transcriptional Regulation in Prokaryotes

Types of regulationPositive Control

• Regulation of gene expression by a regulatory protein called activator protein.

• Activator protein – allows transcription

Negative Control• Regulation of gene

expression by a regulatory protein called repressor protein.

• Repressor protein – hinders transcription

Types of Genes(based on the small effector molecules)

Inducible Genes• Genes that are transcriptionally

regulated by an inducer.• Inducer – a small effector

molecule that binds to:– an activator protein which

allows binding of the protein to the DNA.

– A repressor protein which hinders binding of the protein to the DNA.

Repressible Genes• Genes that are transcriptionally

regulated either by a corepressor or an inhibitor.

• Corepressor – a small effector molecule which binds to a repressor protein that allows binding of the protein to the DNA.

• Inhibitor – a small effector molecule which binds to an activator protein that restricts binding of the protein to the DNA.

Inducible genes

Repressible genes

Operon

Definition and Discovery

Definition• Refers to two or more

contigious genes and the genetic elements that regulate their transcription in a coordinate fashion

• Consists of promoter, operator, and structural genes

• Encodes proteins (enzymes) that have common function

Discovery• François Jacob and Jacques

Monod (1940)• Via combination of

biochemical and genetic analyses

Lac Operon

Lactose operon• First operon to be discovered• François Jacob and Jacques Monod (1940)

• Contains three genes that codes for proteins involved in lactose metabolism in Escherichia coli that plays a role in bacterial growth

• It is said to be inducible– Due to its inducer “Lactose”

Components of the Lac Region

• Regulatory gene (LacI)– Expresses the Lac repressor• A regulatory protein of Lac Operon• Responsible for the Negative Control of Lac Operon

• Lac Operon– CAP site

• The binding site of CAP–Catabolite Activator Protein–Another regulatory protein of Lac Operon–Responsible for the Positive Control of lac Operon

(Continuation)– LacP

• Binding site of RNA Polymerase

– LacO• Binding site of Lac repressor

– LacZ• Encodes β-galactosidase

– LacY• Encodes lactose permease

– LacA• Encodes galactoside transacetylase

Lactose metabolism in Escherichia coli

• Involves the three enzymes expressed by the lac operon– β-galactosidase

• Catalyzes Lactose → Glucose + Galactose• Catalyzes Lactose → Allolactose (side reaction)

– Lactose permease• Serves as the channel protein of lactose to the cell

– Galactoside transacetylase• Acetylation of lactose and lac analogs

Regulation of Lac Operon

Negative Control• Allosteric regulation• Lac Repressor– Responsible for the negative control of lac operon– Presence of lactose and lac analogs

• Binding to the allosteric site• Conformational change in the active site• Hindrance of lac repressor binding• Transcription occurs

– Absence of lactose and lac analogs• Binding of lac repressor = No Transcription

Positive Control• Catabolite repression• CAP– Catabolite Activator Protein• Responsible for the positive control of lac operon• Activated by cAMP (Cyclic Adenosine

Monophosphate)• Can be deactivated by glucose

– Inhibits adenylyl cyclase via glucose transport and a signalling pathway

– Adenylyl cyclase catalyzes the conversion of ATP to cAMP

References

• Weaver RF. 2012. Molecular Biology 5th Ed. New York: McGraw-Hill. 914 P.

• Karp G. 2010. Cell and Molecular Biology: Concepts and Experiments 6th ed. New Jersey: John Wiley & Sons, Inc. 837 P.

• Brooker RJ. 2012. Genetics: Analysis & Principles 4th Ed. New York: McGraw-Hill. 868 P.

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