The 11S regulators of 20S proteasome activity.
Although substantial progress has been made in understanding the biochemical properties of 11S regulators since their discovery in 1992, we still only have a rudimentary understanding of their biological role. As discussed above, we have proposed a model in which the alpha/beta complex promotes the production of antigenic peptides by opening the exit port of the 20S proteasome (Whitby et al. 2000). There are other possibilities, however, that are not exclusive of the exit port hypothesis. For example the alpha/beta complex may promote assembly of immunoproteasome as suggested by Preckel et al. 1999, or it may function as a docking module and conduit for the delivery of peptides to the ER lumen (Realini et al. 1994b). There are also unanswered structural and mechanistic questions. Higher resolution data are needed to discern important structural details of the PA26/20S proteasome complex. The models for binding and activation that are suggested from the structural data have to be tested by mutagenesis and biochemical analysis. What is the role of homolog-specific inserts? Will cognate regulator/proteasome complexes show conformational changes that are not apparent in the currently available crystal structures, including perhaps signs of allosteric communication between the regulator and the proteasome active sites?
Hill
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Biochemistry Department, University of Utah Medical School, 50 N Medical Drive, Salt Lake City, UT 84132, USA.
Masters
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Whitby
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D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000502:physiology*; D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D001665:Binding Sites; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D010450:Endopeptidases / Q000737:chemistry / Q000502:physiology*; D004789:Enzyme Activation; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D046911:Macromolecular Substances; D009097:Multienzyme Complexes; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C119011:26S proteasome non-ATPase regulatory subunit 13; D000251:Adenosine Triphosphatases