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Figure 1 Protein Triage System

Because of translational or post-translational damage, proteins can become misfolded, leading to surface exposure of hydrophobic regions. These regions are recognition sites for chaperones, which aim at restoring the native protein structure or triage to the ubiquitin-proteasome system (UPS). This system can also recognize damaged proteins directly and mediates the attachment of at least 4 ubiquitin molecules, which directs proteins to degradation by the proteasome. Deubiquitinating enzymes can reverse the ubiquitin-chain degradation signal, and damaged proteins receive a new chance for refolding. Some proteins, such as oxidatively damaged proteins, can be recognized directly by the proteasome complex. A protein's propensity to fold to a state with particular binding characteristics, including the affinity for chaperones versus proteases, will determine its fate. This includes restoration of protein structure and function, protein degradation, and protein cross-linking and aggregation.