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Molecular machines for protein degradation

Journal

CHEMBIOCHEM
Volume 6, Issue 2, Pages 222-256

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.200400313

Keywords

molecular machines; proteasomes; protein degradation; protein structures; structure-activity relationships

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One of the most precisely regulated processes in living cells is intracellular protein degradation. The main component of the degradation machinery is the 20S proteasome present in both eukaryotes and prokaryotes. In addition, there exist other proteasome-related protein-degradation machineries, like HsIVU in eubacteria. Peptides generated by proteosomes and related systems can be used by the cell, for example, for antigen presentation. However, most of the peptides must be degraded to single amino acids, which ore further used in cell metabolism and for the synthesis of new proteins. Tricorn protease and its interacting factors are working downstream of the proteasome and process the peptides into amino acids. Here, we summarise the current state of knowledge about protein-degradation systems, focusing in particular on the proteosome, HsIVU, Tricorn protease and its interacting factors and DegP The structural information about these protein complexes opens new possibilities for identifying, characterising. and elucidating the mode of action of natural and synthetic inhibitors, which affects their function. Some of these compounds may find therapeutic applications in contemporary medicine.

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