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Dissection of the mechanism for the stringent factor RelA
Thomas M Wendrich1, Gregor Blaha, Daniel N Wilson
1Fachbereich Chemie-Biochemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse, D-35032, Marburg, Germany.
Molecular Cell
|November 7, 2002
Summary
The stringent factor RelA binds to blocked ribosomes during nutrient deprivation. Its binding affinity decreases upon synthesizing (p)ppGpp, explaining how low RelA levels monitor ribosome starvation.
Area of Science:
- Molecular Biology
- Bacterial Physiology
- Ribosome Function
Background:
- Nutrient deprivation triggers ribosome stalling by uncharged tRNA.
- This stalling activates the stringent factor RelA to produce (p)ppGpp, initiating the stringent response.
Purpose of the Study:
- To investigate the binding dynamics of RelA to ribosomes.
- To elucidate the mechanism of (p)ppGpp synthesis regulation by RelA.
Main Methods:
- In vitro biochemical assays to study RelA-ribosome interactions.
- Analysis of RelA binding and (p)ppGpp synthesis under varying conditions.
Main Results:
- RelA binding to ribosomes is primarily mediated by mRNA, independent of ribosomal protein L11.
- (p)ppGpp synthesis requires uncharged tRNA at the ribosome's A site and ribosomal protein L11.
- RelA binding and (p)ppGpp synthesis are inversely coupled; synthesis reduces RelA's affinity for the ribosome.
Conclusions:
- A model of RelA "hopping" between stalled ribosomes explains efficient (p)ppGpp production.
- This mechanism allows low intracellular RelA concentrations to accurately reflect the extent of ribosome stalling and nutrient stress.