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Published on: July 8, 2019
Dynamic allostery in the methionine repressor revealed by force distribution analysis
Wolfram Stacklies1, Fei Xia, Frauke Gräter
1CAS-MPG Partner Institute for Computational Biology, Key laboratory of Computational Biology, Chinese Academy of Sciences, Shanghai, China.
Plos Computational Biology
|November 26, 2009
Summary
Protein allostery regulates gene expression. Force distribution analysis reveals how SAM binding to methionine repressor MetJ quenches dynamics, enabling DNA binding through a molecular network.
Area of Science:
- Biochemistry and Molecular Biology
- Structural Biology
- Computational Biology
Background:
- Allosteric regulation is crucial for fundamental cellular processes like gene expression.
- Long-range communication mechanisms in allostery are not fully understood.
- Methionine repressor MetJ activation by SAM is a model for studying allostery.
Purpose of the Study:
- To elucidate the molecular mechanism of allosteric signal propagation in MetJ.
- To investigate how SAM binding regulates MetJ dynamics despite minimal conformational changes.
- To introduce force distribution analysis as a tool for studying allosteric proteins.
Main Methods:
- Molecular dynamics (MD) simulations of the methionine repressor MetJ.
- Analysis of correlated domain motions and conformational fluctuations.
- Direct monitoring of internal force propagation using force distribution analysis.
Main Results:
- SAM binding to MetJ quenches correlated domain motions, entropically favoring DNA binding.
- Force distribution analysis identified a molecular network for strain propagation through the protein core.
- Specific parts of this network are directly influenced by SAM binding, explaining the observed dynamics quenching.
Conclusions:
- Force distribution analysis provides direct insight into allosteric signal transmission.
- This method reveals the molecular network underlying MetJ's response to SAM.
- The findings offer a new perspective on the function of allosteric proteins.
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