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Structural Basis for the Processive Protein Degradation by Tricorn Protease

  • H. Brandstetter , J.-S. Kim , M. Groll , P. Göttig and R. Huber
Published/Copyright: June 1, 2005
Biological Chemistry
From the journal Volume 383 Issue 7-8

Abstract

Cell survival critically depends on the efficient use of available resources. This includes both the clearance and the recycling of those protein components that have become futile or defective. Several proteins sequentially accomplish this complex task. The proteasome serves as an initial protein shredder and generates peptides of 7 12 amino acids in length. In general, these products are useless burden to the cell and need further processing. A few years ago, a proteolytic system was identified in the model organism Thermoplasma acidophilum which indeed performs this processing [Tamura et al., Science 274 (1996), 1385 1389]. The hexameric core protein of this modular system, referred to as tricorn protease, is a 720 kDa protease which is able to assemble further into a giant icosahedral capsid, as determined by electron microscopy. Recently, we determined the crystal structure of the tricorn core particle at 2.0 å resolution [Brandstetter et al., Nature 414 (2001), 466 469]. Here we describe the structural and mechanistic basis for tricorns processive degradation mode, including a novel electrostatic substratetoproduct sink, and suggest how further components might interact with the tricorn protease to complete the cellular waste recycling process.

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Published Online: 2005-06-01
Published in Print: 2002-08-27

Copyright © 2002 by Walter de Gruyter GmbH & Co. KG

Articles in the same Issue

  1. The International Proteolysis Society (IPS): A Society for Proteolysis, Proteases and Protease Inhibitors
  2. Proteases and Their Inhibitors: Traditional Research Subjects in the Munich Area
  3. Apoptotic Pathways: Involvement of Lysosomal Proteases
  4. Human Tissue Kallikreins: A New Enzymatic Cascade Pathway?
  5. Discovery of Chemokine Substrates for Matrix Metalloproteinases by Exosite Scanning: A New Tool for Degradomics
  6. Novel Secretory Vesicle Serpins, Endopin 1 and Endopin 2: Endogenous Protease Inhibitors with Distinct Target Protease Specificities
  7. Extracellular Proteases of Staphylococcus spp.
  8. Secreted Aspartic Proteases as Virulence Factors of Candida Species
  9. Triple-Helical Peptide Analysis of Collagenolytic Protease Activity
  10. Phage Display Substrate: A Blind Method for Determining Protease Specificity
  11. Evolution of Placental Proteases
  12. Factor VII Activating Protease (FSAP): A Novel Protease in Hemostasis
  13. Cold-Adapted and Mesophilic Brachyurins
  14. The Role of Dipeptidyl Peptidase IV (DP IV) Enzymatic Activity in T Cell Activation and Autoimmunity
  15. Biochemical Features, Molecular Biology and Clinical Relevance of the Human 15-Domain Serine Proteinase Inhibitor LEKTI
  16. Interaction of Plasminogen Activator Inhibitor Type-1 (PAI-1) with Vitronectin (Vn): Mapping the Binding Sites on PAI-1 and Vn
  17. Structure-Function Relationship of Bromelain Isoinhibitors from Pineapple Stem
  18. Structural Basis for the Processive Protein Degradation by Tricorn Protease
  19. Zinc Ligands in an Astacin Family Metalloprotease Meprin A
  20. Probing the Active Sites and Mechanisms of Rat Metalloproteases Meprin A and B
  21. (R)-3-Amidinophenylalanine-Derived Inhibitors of Factor Xa with a Novel Active-Site Binding Mode
  22. Inhibition of Arginine Gingipains (RgpB and HRgpA) with Benzamidine Inhibitors: Zinc Increases Inhibitory Potency
  23. Cathepsin B Stability, But Not Activity, Is Affected in Cysteine:Cystine Redox Buffers
  24. Inhibition of Mammalian Legumain by Michael Acceptors and AzaAsn-Halomethylketones
  25. Role of the Prosegment of Fasciola hepatica Cathepsin L1 in Folding of the Catalytic Domain
  26. Roles for Arg- and Lys-Gingipains in the Disruption of Cytokine Responses and Loss of Viability of Human Endothelial Cells by Porphyromonas gingivalis Infection
  27. Aberrant Expression of Serpin Squamous Cell Carcinoma Antigen 2 in Human Tumor Tissues and Cell Lines: Evidence of Protection from Tumor Necrosis Factor-Mediated Apoptosis
  28. Endosomal-Lysosomal Proteolysis Mediates Death Signalling by TNFα, Not by Etoposide, in L929 Fibrosarcoma Cells: Evidence for an Active Role of Cathepsin D
  29. Anti-Inflammatory Effect of Pre-Elafin in Lipopolysaccharide-Induced Acute Lung Inflammation
  30. The 26S Proteasome Rpn10 Gene Encoding Splicing Isoforms: Evolutional Conservation of the Genomic Organization in Vertebrates
  31. Reverse Genetic Analysis of the Caenorhabditis elegans 26S Proteasome Subunits by RNA Interference
  32. Purification and Characterization of the 20S Proteasome from Ostrich Skeletal Muscle
  33. Identification of a Signal Transduction Pathway That Regulates MMP-9 mRNA Expression in Glomerular Injury
  34. Modulation of the Endosomal and Lysosomal Distribution of Cathepsins B, L and S in Human Monocytes/Macrophages
  35. Characterization of Novel Anti-Cathepsin W Antibodies and Cellular Distribution of Cathepsin W in the Gastrointestinal Tract
  36. Functional Consequences of Cathepsin L Deficiency in Human Lung Epithelial Cells
  37. Determination of Cathepsin B Expression May Offer Additional Prognostic Information for Ovarian Cancer Patients
  38. CA-074, But Not Its Methyl Ester CA-074Me, Is a Selective Inhibitor of Cathepsin B within Living Cells
  39. Trypsin Mutants for Structure-Based Drug Design: Expression, Refolding and Crystallisation
https://doi.org/10.1515/BC.2002.127

Articles in the same Issue

  1. The International Proteolysis Society (IPS): A Society for Proteolysis, Proteases and Protease Inhibitors
  2. Proteases and Their Inhibitors: Traditional Research Subjects in the Munich Area
  3. Apoptotic Pathways: Involvement of Lysosomal Proteases
  4. Human Tissue Kallikreins: A New Enzymatic Cascade Pathway?
  5. Discovery of Chemokine Substrates for Matrix Metalloproteinases by Exosite Scanning: A New Tool for Degradomics
  6. Novel Secretory Vesicle Serpins, Endopin 1 and Endopin 2: Endogenous Protease Inhibitors with Distinct Target Protease Specificities
  7. Extracellular Proteases of Staphylococcus spp.
  8. Secreted Aspartic Proteases as Virulence Factors of Candida Species
  9. Triple-Helical Peptide Analysis of Collagenolytic Protease Activity
  10. Phage Display Substrate: A Blind Method for Determining Protease Specificity
  11. Evolution of Placental Proteases
  12. Factor VII Activating Protease (FSAP): A Novel Protease in Hemostasis
  13. Cold-Adapted and Mesophilic Brachyurins
  14. The Role of Dipeptidyl Peptidase IV (DP IV) Enzymatic Activity in T Cell Activation and Autoimmunity
  15. Biochemical Features, Molecular Biology and Clinical Relevance of the Human 15-Domain Serine Proteinase Inhibitor LEKTI
  16. Interaction of Plasminogen Activator Inhibitor Type-1 (PAI-1) with Vitronectin (Vn): Mapping the Binding Sites on PAI-1 and Vn
  17. Structure-Function Relationship of Bromelain Isoinhibitors from Pineapple Stem
  18. Structural Basis for the Processive Protein Degradation by Tricorn Protease
  19. Zinc Ligands in an Astacin Family Metalloprotease Meprin A
  20. Probing the Active Sites and Mechanisms of Rat Metalloproteases Meprin A and B
  21. (R)-3-Amidinophenylalanine-Derived Inhibitors of Factor Xa with a Novel Active-Site Binding Mode
  22. Inhibition of Arginine Gingipains (RgpB and HRgpA) with Benzamidine Inhibitors: Zinc Increases Inhibitory Potency
  23. Cathepsin B Stability, But Not Activity, Is Affected in Cysteine:Cystine Redox Buffers
  24. Inhibition of Mammalian Legumain by Michael Acceptors and AzaAsn-Halomethylketones
  25. Role of the Prosegment of Fasciola hepatica Cathepsin L1 in Folding of the Catalytic Domain
  26. Roles for Arg- and Lys-Gingipains in the Disruption of Cytokine Responses and Loss of Viability of Human Endothelial Cells by Porphyromonas gingivalis Infection
  27. Aberrant Expression of Serpin Squamous Cell Carcinoma Antigen 2 in Human Tumor Tissues and Cell Lines: Evidence of Protection from Tumor Necrosis Factor-Mediated Apoptosis
  28. Endosomal-Lysosomal Proteolysis Mediates Death Signalling by TNFα, Not by Etoposide, in L929 Fibrosarcoma Cells: Evidence for an Active Role of Cathepsin D
  29. Anti-Inflammatory Effect of Pre-Elafin in Lipopolysaccharide-Induced Acute Lung Inflammation
  30. The 26S Proteasome Rpn10 Gene Encoding Splicing Isoforms: Evolutional Conservation of the Genomic Organization in Vertebrates
  31. Reverse Genetic Analysis of the Caenorhabditis elegans 26S Proteasome Subunits by RNA Interference
  32. Purification and Characterization of the 20S Proteasome from Ostrich Skeletal Muscle
  33. Identification of a Signal Transduction Pathway That Regulates MMP-9 mRNA Expression in Glomerular Injury
  34. Modulation of the Endosomal and Lysosomal Distribution of Cathepsins B, L and S in Human Monocytes/Macrophages
  35. Characterization of Novel Anti-Cathepsin W Antibodies and Cellular Distribution of Cathepsin W in the Gastrointestinal Tract
  36. Functional Consequences of Cathepsin L Deficiency in Human Lung Epithelial Cells
  37. Determination of Cathepsin B Expression May Offer Additional Prognostic Information for Ovarian Cancer Patients
  38. CA-074, But Not Its Methyl Ester CA-074Me, Is a Selective Inhibitor of Cathepsin B within Living Cells
  39. Trypsin Mutants for Structure-Based Drug Design: Expression, Refolding and Crystallisation
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