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A microbial sensor for discovering structural probes of protein misfolding and aggregation.
- Source :
-
Prion [Prion] 2013 Mar-Apr; Vol. 7 (2), pp. 151-6. Date of Electronic Publication: 2013 Jan 28. - Publication Year :
- 2013
-
Abstract
- In all cell types, protein homeostasis, or "proteostasis," is maintained by sophisticated quality control networks that regulate protein synthesis, folding, trafficking, aggregation, disaggregation, and degradation. In one notable example, Escherichia coli employ a proteostasis system that determines whether substrates of the twin-arginine translocation (Tat) pathway are correctly folded and thus suitable for transport across the tightly sealed cytoplasmic membrane. Herein, we review growing evidence that the Tat translocase itself discriminates folded proteins from those that are misfolded and/or aggregated, preferentially exporting only the former. Genetic suppressors that inactivate this mechanism have recently been isolated and provide direct evidence for the participation of the Tat translocase in structural proofreading of its protein substrates. We also discuss how this discriminatory "folding sensor" has been exploited for the discovery of structural probes (e.g., sequence mutations, pharmacologic chaperones, intracellular antibodies) that modulate the folding and solubility of virtually any protein-of-interest, including those associated with aggregation diseases (e.g., α-synuclein, amyloid-β protein). Taken together, these studies highlight the utility of engineered bacteria for rapidly and inexpensively uncovering potent anti-aggregation factors.
- Subjects :
- Amyloid metabolism
Antibodies metabolism
Biotechnology
Escherichia coli metabolism
Escherichia coli Proteins chemistry
Escherichia coli Proteins metabolism
High-Throughput Screening Assays
Intracellular Space chemistry
Intracellular Space metabolism
Membrane Transport Proteins chemistry
Membrane Transport Proteins metabolism
Models, Molecular
Molecular Probe Techniques
Protein Binding
Protein Folding
Amyloid analysis
Biosensing Techniques methods
Subjects
Details
- Language :
- English
- ISSN :
- 1933-690X
- Volume :
- 7
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Prion
- Publication Type :
- Academic Journal
- Accession number :
- 23357829
- Full Text :
- https://doi.org/10.4161/pri.23328