PMID:23219534
| Citation |
Bershtein, S, Mu, W, Serohijos, AW, Zhou, J and Shakhnovich, EI (2013) Protein quality control acts on folding intermediates to shape the effects of mutations on organismal fitness. Mol. Cell 49:133-44 |
|---|---|
| Abstract |
What are the molecular properties of proteins that fall on the radar of protein quality control (PQC)? Here we mutate the E. coli's gene encoding dihydrofolate reductase (DHFR) and replace it with bacterial orthologous genes to determine how components of PQC modulate fitness effects of these genetic changes. We find that chaperonins GroEL/ES and protease Lon compete for binding to molten globule intermediate of DHFR, resulting in a peculiar symmetry in their action: overexpression of GroEL/ES and deletion of Lon both restore growth of deleterious DHFR mutants and most of the slow-growing orthologous DHFR strains. Kinetic steady-state modeling predicts and experimentation verifies that mutations affect fitness by shifting the flux balance in cellular milieu between protein production, folding, and degradation orchestrated by PQC through the interaction with folding intermediates. |
| Links |
PubMed PMC3545112 Online version:10.1016/j.molcel.2012.11.004 |
| Keywords |
Algorithms; Amino Acid Motifs; Base Sequence; Chaperonin 10/genetics; Chaperonin 10/metabolism; Chaperonin 60/genetics; Chaperonin 60/metabolism; Escherichia coli/enzymology; Escherichia coli/genetics; Escherichia coli/growth & development; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Gene Expression Regulation, Bacterial; Gene Knockout Techniques; Genetic Fitness; Homeostasis; Kinetics; Microbial Viability; Models, Biological; Molecular Sequence Data; Mutation, Missense; Protease La/genetics; Protease La/metabolism; Protein Biosynthesis; Protein Folding; Proteolysis; Tetrahydrofolate Dehydrogenase/chemistry; Tetrahydrofolate Dehydrogenase/genetics; Tetrahydrofolate Dehydrogenase/metabolism |
| edit table |
Significance
You can help EcoliWiki by summarizing why this paper is useful
Useful Materials and Methods
You can help Ecoliwiki by describing the useful materials (strains, plasmids, antibodies, etc) described in this paper.
Annotations
<annotationlinks/>
EcoliWiki Links
Add links to pages that link here (e.g. gene, product, method pages)
See also
References
See Help:References for how to manage references in EcoliWiki.