title: Molecular machines for protein degradation.
abstract: 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 HslVU in eubacteria. Peptides generated by proteasomes 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 are 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 proteasome, HslVU, 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.
authors.affiliation: Adolf-Butenandt-Institut Physiological Chemistry, LMU München, Butenandtstrasse 5, Gebäude B, 81377 München, Germany. michael.groll@bio.med.uni-muenchen.de
authors.forename: Michael
authors.initials: M
authors.lastname: Groll
authors.forename: Matthias
authors.initials: M
authors.lastname: Bochtler
authors.forename: Hans
authors.initials: H
authors.lastname: Brandstetter
authors.forename: Tim
authors.initials: T
authors.lastname: Clausen
authors.forename: Robert
authors.initials: R
authors.lastname: Huber
mesh_terms: D049069:ATP-Dependent Proteases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D046912:Multiprotein Complexes; D033903:Periplasmic Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D061988:Proteasome Inhibitors; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D033903:Periplasmic Proteins; D061988:Proteasome Inhibitors; D021122:Protein Subunits; D010450:Endopeptidases; C102094:tricorn protease; D018819:Dipeptidyl Peptidase 4; D049069:ATP-Dependent Proteases; C061682:DegP protease; D012697:Serine Endopeptidases; D046988:Proteasome Endopeptidase Complex