Abstract
Tripeptidyl peptidase II is the largest known eukaryotic peptidase. It has been described as a multi-purpose peptidase, which, in addition to its house-keeping function in intracellular protein degradation, plays a role in several vital cellular processes such as antigen processing, apoptosis, or cell division, and is involved in diseases like muscle wasting, obesity, and in cancer. Biochemical studies and bioinformatics have identified TPPII as a subtilase, but its structure is very unusual: it forms a large homooligomeric complex (6 MDa) with a spindle-like shape. Recently, the high-resolution structure of TPPII homodimers (300 kDa) was solved and a hybrid structure of the holocomplex built of 20 dimers was obtained by docking it into the EM-density. Here, we summarize our current knowledge about TPPII with a focus on structural aspects. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome.
Copyright © 2011 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Amino Acid Sequence
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Aminopeptidases / chemistry*
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Aminopeptidases / genetics
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Aminopeptidases / metabolism
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Aminopeptidases / physiology*
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Animals
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Cytosol / enzymology
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Cytosol / metabolism
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / chemistry*
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / genetics
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / metabolism
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / physiology*
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Humans
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Models, Biological
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Models, Molecular
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Molecular Sequence Data
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Peptide Hydrolases / chemistry
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Peptide Hydrolases / metabolism
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Peptide Hydrolases / physiology
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Phylogeny
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Protein Conformation
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Proteolysis
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Sequence Homology, Amino Acid
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Serine Endopeptidases / chemistry*
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Serine Endopeptidases / genetics
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Serine Endopeptidases / metabolism
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Serine Endopeptidases / physiology*
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Structure-Activity Relationship
Substances
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Peptide Hydrolases
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Aminopeptidases
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
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tripeptidyl-peptidase 2
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Serine Endopeptidases