PMID:23201899
| Citation |
Mauldin, RV and Sauer, RT (2013) Allosteric regulation of DegS protease subunits through a shared energy landscape. Nat. Chem. Biol. 9:90-6 |
|---|---|
| Abstract |
The PDZ domains of the trimeric DegS protease bind unassembled outer-membrane proteins (OMPs) that accumulate in the Escherichia coli periplasm. This cooperative binding reaction triggers a proteolytic cascade that activates a transcriptional stress response. To dissect the mechanism of allosteric activation, we generated hybrid DegS trimers with different numbers of PDZ domains and/or protease-domain mutations. By studying the chemical reactivity and enzymatic properties of these hybrids, we show that all subunits experience a strongly coupled energetic landscape. For example, OMP peptide binding to a single PDZ domain stimulates active site chemical modification and proteolytic cleavage in the attached and neighboring protease domains. OMP peptide binding relieves inhibitory PDZ interactions, whereas the interfaces between protease domains in the trimeric DegS core mediate positively cooperative activation driven by both substrate binding and inhibition relief. |
| Links |
PubMed PMC3551985 Online version:10.1038/nchembio.1135 |
| Keywords |
Allosteric Site; Catalytic Domain; Dimerization; Dose-Response Relationship, Drug; Escherichia coli/enzymology; Escherichia coli Proteins/biosynthesis; Gene Expression Regulation, Bacterial; Kinetics; Models, Biological; Molecular Conformation; Mutation; Peptides/chemistry; Protein Conformation; Protein Structure, Tertiary; Thermodynamics |
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