Protein quality control (QC) pathways survey the cellular proteome to selectively recognize and degrade faulty proteins whose accumulation can lead to various diseases. Recognition of the occasional aberrant protein among an abundant sea of similar normal counterparts poses a considerable challenge to the cell. Solving this problem requires protein QC machinery to assay multiple molecular criteria within a spatial and temporal context. Although each QC pathway has unique criteria and mechanisms for distinguishing right from wrong, they appear to share several general concepts. We discuss principles of high-fidelity target recognition, the decisive event of all protein QC pathways, to guide future work in this area.
Keywords: chaperone; degradation; protein misfolding; triage; ubiquitination.
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