MCB 150 Lecture 33: Regulation in Bacteria and Eukaryotes

Regulation in Bacteria

• Levels of β-gal, permease, and transacetylase can be adjusted post-transcriptionally.

• The ratio of protein products is 10:5:2 (β-gal : permease : transacetylase).

  • This precise ratio is crucial for the coordinated function of these enzymes in lactose metabolism.

Adjustments from a Single mRNA

1. mRNA Stability

   • Bacterial mRNAs have rapid turnover with a half-life of approximately 2 minutes.

     • This rapid degradation is due to factors like RNases and structural elements in the mRNA.

   • This allows for a quick response to environmental changes.

     • When environmental conditions change, bacteria can quickly alter gene expression by degrading existing mRNAs and synthesizing new ones.

   • The lac mRNA is degraded from the 3' end, which contributes to the protein ratio.

     • The 3' end degradation exposes different genes at different rates, affecting the final protein product ratio.

2. Translation Initiation

   • The "strength" of the Shine-Dalgarno sequence affects protein production.

     • A strong Shine-Dalgarno sequence ensures efficient ribosome binding and translation initiation.

   • A sequence closer to the consensus results in more protein synthesis.

     • The closer the sequence is to the consensus (AGGAGG), the more effectively the ribosome binds.

   • The Shine-Dalgarno sequence availability can be influenced by proteins or secondary structures.

     • Proteins can bind to the mRNA and either expose or block the Shine-Dalgarno sequence.

     • Secondary structures like stem-loops can hide the Shine-Dalgarno sequence, reducing translation.

Operons

• The lac operon is inducible; it can be turned on when needed.

  • In the absence of lactose, a repressor protein binds to the operator region, preventing transcription.

  • When lactose is present, it is converted to allolactose, which binds to the repressor, causing it to detach from the operator and allowing transcription.

• The tryptophan (trp) operon is on by default and repressible.

  • It can be turned off when tryptophan is abundant.

    • When tryptophan levels are high, tryptophan binds to the trp repressor, activating it.

    • The activated repressor then binds to the operator, blocking further transcription of the trp operon.

Other Regulation of Protein Activity

• Allosteric regulation or feedback inhibition of proteins (e.g., regulation of PFK in glycolysis).

  • In allosteric regulation, a small molecule binds to an enzyme, changing its shape and activity.

  • Feedback inhibition is a type of allosteric regulation where the end product of a metabolic pathway inhibits an enzyme in the pathway.

Regulation Level Considerations

• Transcriptional regulation saves the most energy.

  • By preventing the synthesis of mRNA, the cell avoids wasting resources on unnecessary protein production.

• Post-translational regulation takes effect faster.

  • Modifying existing proteins allows for an immediate response to cellular signals.

• Regulation at different levels is balanced to produce the correct amount of functional protein under given conditions.

  • Cells use a combination of regulatory mechanisms to fine-tune protein levels and activities, ensuring efficient and appropriate responses to various stimuli.

Transcriptional Control in Eukary