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Background: Oligopeptidases are serine proteases cleaving only short peptides. Results: The complex channel system found within a hexameric oligopeptidase presents a rigid, double-gated model for size-based substrate selection. Conclusion:The substrate selection mechanism applied by an oligopeptidase depends on its multimerization state. Significance: Degradation of cytotoxic and misfolded proteins is aided by oligopeptidases, which are thus possible targets of cancer therapy.

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