title: Structure and function of tripeptidyl peptidase II, a giant cytosolic protease.
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.
authors.affiliation: Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Martinsried, Germany. rockel@biochem.mpg.de
authors.forename: Beate
authors.initials: B
authors.lastname: Rockel
authors.forename: Klaus O
authors.initials: KO
authors.lastname: Kopec
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Lupas
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumeister
mesh_terms: D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D010802:Phylogeny; D011487:Protein Conformation; D059748:Proteolysis; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D010447:Peptide Hydrolases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C048001:tripeptidyl-peptidase 2; D012697:Serine Endopeptidases