Molecular Machines for Protein Degradation

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.

[1]  R. Huber,et al.  Binding Mode of TMC‐95A Analogues to Eukaryotic 20S Proteasome , 2004, Chembiochem : a European journal of chemical biology.

[2]  Robert M. Williams,et al.  A concise, total synthesis of the TMC-95A/B proteasome inhibitors. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[3]  A. Wlodawer,et al.  Crystal structure of the AAA + a domain of E . coli Lon protease at 1 . 9 A resolution , 2003 .

[4]  A. Wlodawer,et al.  The Catalytic Domain of Escherichia coli Lon Protease Has a Unique Fold and a Ser-Lys Dyad in the Active Site* , 2004, Journal of Biological Chemistry.

[5]  W. Baumeister,et al.  Crystal structures of the Rhodococcus proteasome with and without its pro-peptides: implications for the role of the pro-peptide in proteasome assembly. , 2004, Journal of molecular biology.

[6]  C. Renner,et al.  TMC‐95A Analogues with Endocyclic Biphenyl Ether Group as Proteasome Inhibitors , 2004, Chemistry & biodiversity.

[7]  W. Baumeister,et al.  Functional analysis of the proteasome regulatory particle , 1999, Molecular Biology Reports.

[8]  S. Wilk,et al.  Synthetic peptide-based activators of the proteasome , 1997, Molecular Biology Reports.

[9]  Dong Young Kim,et al.  Crystal Structure of ClpX Molecular Chaperone from Helicobacter pylori* , 2003, Journal of Biological Chemistry.

[10]  W. Houry,et al.  Solution Structure of the Dimeric Zinc Binding Domain of the Chaperone ClpX* , 2003, Journal of Biological Chemistry.

[11]  M. Groll,et al.  Molecular shredders: how proteasomes fulfill their role. , 2003, Current opinion in structural biology.

[12]  M. Bycroft,et al.  Structure of the Jab1/MPN domain and its implications for proteasome function. , 2003, Biochemistry.

[13]  M. Kaiser,et al.  Synthesis of a TMC-95A ketomethylene analogue by cyclization via intramolecular Suzuki coupling. , 2003, Organic letters.

[14]  D. Schneider,et al.  Sequential recognition of two distinct sites in σS by the proteolytic targeting factor RssB and ClpX , 2003, The EMBO journal.

[15]  B. Bukau,et al.  Targeted delivery of an ssrA-tagged substrate by the adaptor protein SspB to its cognate AAA+ protein ClpX. , 2003, Molecular cell.

[16]  T. Baker,et al.  Structure of a delivery protein for an AAA+ protease in complex with a peptide degradation tag. , 2003, Molecular cell.

[17]  D. Mckay,et al.  Structure and reactivity of an asymmetric complex between HslV and I-domain deleted HslU, a prokaryotic homolog of the eukaryotic proteasome. , 2003, Journal of molecular biology.

[18]  M. Eck,et al.  Structural basis of degradation signal recognition by SspB, a specificity-enhancing factor for the ClpXP proteolytic machine. , 2003, Molecular cell.

[19]  S. Eom,et al.  Molecular architecture of the ATP‐dependent CodWX protease having an N‐terminal serine active site , 2003, The EMBO journal.

[20]  R. Huber,et al.  Substrate access and processing by the 20S proteasome core particle. , 2003, The international journal of biochemistry & cell biology.

[21]  Yi-Ying Lee,et al.  Subunit Oligomerization and Substrate Recognition of the Escherichia coli ClpYQ (HslUV) Protease Implicated by In Vivo Protein-Protein Interactions in the Yeast Two-Hybrid System , 2003, Journal of bacteriology.

[22]  Robert Huber,et al.  The crystal structure of dipeptidyl peptidase IV (CD26) reveals its functional regulation and enzymatic mechanism , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[23]  R. Huber,et al.  Investigations on the maturation and regulation of archaebacterial proteasomes. , 2003, Journal of molecular biology.

[24]  S. Smith‐Gill,et al.  Dissection of binding interactions in the complex between the anti-lysozyme antibody HyHEL-63 and its antigen. , 2003, Biochemistry.

[25]  R. Huber,et al.  Isolation and characterization of the prokaryotic proteasome homolog HslVU (ClpQY) from Thermotoga maritima and the crystal structure of HslV. , 2002, Biophysical chemistry.

[26]  Jimin Wang.  A second response in correcting the HslV-HslU quaternary structure. , 2003, Journal of structural biology.

[27]  A. Goldberg,et al.  ATP hydrolysis by the proteasome regulatory complex PAN serves multiple functions in protein degradation. , 2003, Molecular cell.

[28]  Sven Branner,et al.  Crystal structure of human dipeptidyl peptidase IV/CD26 in complex with a substrate analog , 2003, Nature Structural Biology.

[29]  Muyang Li,et al.  Crystal Structure of a UBP-Family Deubiquitinating Enzyme in Isolation and in Complex with Ubiquitin Aldehyde , 2002, Cell.

[30]  R. Huber,et al.  Navigation inside a protease: substrate selection and product exit in the tricorn protease from Thermoplasma acidophilum. , 2002, Journal of molecular biology.

[31]  J. Dujardin,et al.  Eubacterial HslV and HslU subunits homologs in primordial eukaryotes. , 2002, Molecular biology and evolution.

[32]  Bernd Bukau,et al.  Structural analysis of the adaptor protein ClpS in complex with the N-terminal domain of ClpA , 2002, Nature Structural Biology.

[33]  L. Esser,et al.  Crystal Structure of the Heterodimeric Complex of the Adaptor, ClpS, with the N-domain of the AAA+ Chaperone, ClpA* , 2002, The Journal of Biological Chemistry.

[34]  L. Esser,et al.  Crystal Structure of ClpA, an Hsp100 Chaperone and Regulator of ClpAP Protease* , 2002, The Journal of Biological Chemistry.

[35]  Wolfgang Baumeister,et al.  A giant protease with a twist: the TPP II complex from Drosophila studied by electron microscopy , 2002, The EMBO journal.

[36]  R. Huber,et al.  Structures of the tricorn‐interacting aminopeptidase F1 with different ligands explain its catalytic mechanism , 2002, The EMBO journal.

[37]  B. Bukau,et al.  AAA+ proteins and substrate recognition, it all depends on their partner in crime , 2002, FEBS letters.

[38]  Masasuke Yoshida,et al.  Hexameric ring structure of the ATPase domain of the membrane-integrated metalloprotease FtsH from Thermus thermophilus HB8. , 2002, Structure.

[39]  B. Bukau,et al.  Protein folding and degradation in bacteria:¶To degrade or not to degrade? That is the question , 2002, Cellular and Molecular Life Sciences CMLS.

[40]  C. Southan,et al.  The HtrA family of proteases: implications for protein composition and cell fate. , 2002, Molecular cell.

[41]  H. Ploegh,et al.  Multiple associated proteins regulate proteasome structure and function. , 2002, Molecular cell.

[42]  L. Aravind,et al.  Role of Rpn11 Metalloprotease in Deubiquitination and Degradation by the 26S Proteasome , 2002, Science.

[43]  Chandra Verma,et al.  The crystal structure of the AAA domain of the ATP-dependent protease FtsH of Escherichia coli at 1.5 A resolution. , 2002, Structure.

[44]  S. Eom,et al.  The C-terminal Tails of HslU ATPase Act as a Molecular Switch for Activation of HslV Peptidase* , 2002, The Journal of Biological Chemistry.

[45]  R. Huber,et al.  Functional interactions of HslV (ClpQ) with the ATPase HslU (ClpY) , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[46]  D. Mckay,et al.  Crystal structure of HslUV complexed with a vinyl sulfone inhibitor: corroboration of a proposed mechanism of allosteric activation of HslV by HslU. , 2002, Journal of molecular biology.

[47]  T. Mizushima,et al.  The structure of the mammalian 20S proteasome at 2.75 A resolution. , 2002, Structure.

[48]  R. Huber,et al.  Probing structural determinants distal to the site of hydrolysis that control substrate specificity of the 20S proteasome. , 2002, Chemistry & biology.

[49]  Robert Huber,et al.  Crystal structure of DegP (HtrA) reveals a new protease-chaperone machine , 2002, Nature.

[50]  Michael Groll,et al.  Das Grundgerüst von TMC-95A als mögliche Leitstruktur für reversible Proteasominhibitoren , 2002 .

[51]  A. Horwich,et al.  ClpS, a substrate modulator of the ClpAP machine. , 2002, Molecular cell.

[52]  R. Huber,et al.  The core structure of TMC-95A is a promising lead for reversible proteasome inhibition. , 2002, Angewandte Chemie.

[53]  S. Danishefsky,et al.  The total synthesis of proteasome inhibitors TMC-95A and TMC-95B: discovery of a new method to generate cis-propenyl amides. , 2002, Angewandte Chemie.

[54]  Stuart L Schreiber,et al.  Diversity-oriented organic synthesis and proteomics. New frontiers for chemistry & biology. , 2002, Chemistry & biology.

[55]  Neil D. Rawlings,et al.  MEROPS: the protease database , 2002, Nucleic Acids Res..

[56]  A. Goldberg,et al.  Proteins are unfolded on the surface of the ATPase ring before transport into the proteasome. , 2001, Molecular cell.

[57]  D. Mckay,et al.  Structure of Haemophilus influenzae HslV protein at 1.9 A resolution, revealing a cation-binding site near the catalytic site. , 2001, Acta crystallographica. Section D, Biological crystallography.

[58]  R. Huber,et al.  Crystal structure of the tricorn protease reveals a protein disassembly line , 2001, Nature.

[59]  J. Wang,et al.  Nucleotide-dependent conformational changes in a protease-associated ATPase HsIU. , 2001, Structure.

[60]  John Calvin Reed,et al.  Molecular chaperone targeting and regulation by BAG family proteins , 2001, Nature Cell Biology.

[61]  H. Ploegh,et al.  A novel active site‐directed probe specific for deubiquitylating enzymes reveals proteasome association of USP14 , 2001, The EMBO journal.

[62]  R. Huber,et al.  The quaternary arrangement of HslU and HslV in a cocrystal: a response to Wang, Yale. , 2001, Journal of structural biology.

[63]  M. Vidal,et al.  A protein–protein interaction map of the Caenorhabditis elegans 26S proteasome , 2001, EMBO reports.

[64]  R. Huber,et al.  Crystal structure of the 20 S proteasome:TMC-95A complex: a non-covalent proteasome inhibitor. , 2001, Journal of molecular biology.

[65]  Chou-Chi H. Li,et al.  Valosin-containing protein is a multi-ubiquitin chain-targeting factor required in ubiquitin–proteasome degradation , 2001, Nature Cell Biology.

[66]  A. Goldberg,et al.  The axial channel of the proteasome core particle is gated by the Rpt2 ATPase and controls both substrate entry and product release. , 2001, Molecular cell.

[67]  C. Georgopoulos,et al.  Structure-Function Analysis of the Zinc-binding Region of the ClpX Molecular Chaperone* , 2001, The Journal of Biological Chemistry.

[68]  J. Wang,et al.  A corrected quaternary arrangement of the peptidase HslV and atpase HslU in a cocrystal structure. , 2001, Journal of structural biology.

[69]  M. Bogyo,et al.  Global analysis of proteasomal substrate specificity using positional-scanning libraries of covalent inhibitors , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[70]  S. Gottesman,et al.  The RssB response regulator directly targets sigma(S) for degradation by ClpXP. , 2001, Genes & development.

[71]  P. Kloetzel,et al.  20S proteasome biogenesis. , 2001, Biochimie.

[72]  T. Baker,et al.  Molecular determinants of complex formation between Clp/Hsp100 ATPases and the ClpP peptidase , 2001, Nature Structural Biology.

[73]  P. Kloetzel,et al.  Ubiquitin and proteasomes: Antigen processing by the proteasome , 2001, Nature Reviews Molecular Cell Biology.

[74]  Holger Sondermann,et al.  Structure of a Bag/Hsc70 Complex: Convergent Functional Evolution of Hsp70 Nucleotide Exchange Factors , 2001, Science.

[75]  Keiji Tanaka,et al.  The ATP‐dependent CodWX (HslVU) protease in Bacillus subtilis is an N‐terminal serine protease , 2001, The EMBO journal.

[76]  J. Wang,et al.  Crystal structures of the HslVU peptidase-ATPase complex reveal an ATP-dependent proteolysis mechanism. , 2001, Structure.

[77]  R. Pederson,et al.  Metabolism of glucagon by dipeptidyl peptidase IV (CD26) , 2001, Regulatory Peptides.

[78]  M. Sheng,et al.  PDZ domains and the organization of supramolecular complexes. , 2001, Annual review of neuroscience.

[79]  R. Huber,et al.  Mutational studies on HslU and its docking mode with HslV. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[80]  Michael R. Maurizi,et al.  ATP-dependent proteases: Docking of components in a bacterial complex , 2000, Nature.

[81]  A. Steven,et al.  Visualization of substrate binding and translocation by the ATP-dependent protease, ClpXP. , 2000, Molecular cell.

[82]  Christine B. Trame,et al.  Crystal and Solution Structures of an HslUV Protease–Chaperone Complex , 2000, Cell.

[83]  C. Hill,et al.  Structural basis for the activation of 20S proteasomes by 11S regulators , 2000, Nature.

[84]  M. Orłowski,et al.  Catalytic activities of the 20 S proteasome, a multicatalytic proteinase complex. , 2000, Archives of biochemistry and biophysics.

[85]  R. Huber,et al.  A gated channel into the proteasome core particle , 2000, Nature Structural Biology.

[86]  R. Misra,et al.  Overexpression of Protease-Deficient DegPS210ARescues the Lethal Phenotype of Escherichia coli OmpF Assembly Mutants in a degP Background , 2000, Journal of bacteriology.

[87]  B. Diner,et al.  Crystal structures of the photosystem II D1 C-terminal processing protease , 2000, Nature Structural Biology.

[88]  V. Fülöp,et al.  Catalysis of serine oligopeptidases is controlled by a gating filter mechanism , 2000, EMBO reports.

[89]  M. Bogyo,et al.  Integration of the ubiquitin-proteasome pathway with a cytosolic oligopeptidase activity. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[90]  P. Kloetzel,et al.  Characterisation of the newly identified human Ump1 homologue POMP and analysis of LMP7(beta 5i) incorporation into 20 S proteasomes. , 2000, Journal of molecular biology.

[91]  Luis Moroder,et al.  Structure of TPR Domain–Peptide Complexes Critical Elements in the Assembly of the Hsp70–Hsp90 Multichaperone Machine , 2000, Cell.

[92]  Kohei Takahashi,et al.  TMC-95A, B, C, and D, novel proteasome inhibitors produced by Apiospora montagnei Sacc. TC 1093. Taxonomy, production, isolation, and biological activities. , 2000, The Journal of antibiotics.

[93]  J. Peng,et al.  Substrate recognition through a PDZ domain in tail-specific protease. , 2000, Biochemistry.

[94]  Robert Huber,et al.  The structures of HslU and the ATP-dependent protease HslU–HslV , 2000, Nature.

[95]  M. Kuroda,et al.  Structures of TMC-95A-D: novel proteasome inhibitors from Apiospora montagnei sacc. TC 1093. , 2000, The Journal of organic chemistry.

[96]  R. Huber,et al.  Crystal Structure of Epoxomicin:20S Proteasome reveals a molecular basis for selectivity of alpha,beta-Epoxyketone Proteasome Inhibitors , 2000 .

[97]  S. Gottesman,et al.  Posttranslational quality control: folding, refolding, and degrading proteins. , 1999, Science.

[98]  W. Baumeister,et al.  Capsids of tricorn protease studied by electron cryomicroscopy. , 1999, Journal of Structural Biology.

[99]  C. Crews,et al.  Towards subunit-specific proteasome inhibitors: synthesis and evaluation of peptide α', β'-epoxyketones , 1999 .

[100]  C. Ponting,et al.  beta-propeller repeats and a PDZ domain in the tricorn protease: predicted self-compartmentalisation and C-terminal polypeptide-binding strategies of substrate selection. , 1999, FEMS microbiology letters.

[101]  R. Huber,et al.  Crystal structure of gingipain R: an Arg‐specific bacterial cysteine proteinase with a caspase‐like fold , 1999, The EMBO journal.

[102]  R. Huber,et al.  The catalytic sites of 20S proteasomes and their role in subunit maturation: a mutational and crystallographic study. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[103]  A. Wilkinson,et al.  Dissecting the Role of a Conserved Motif (the Second Region of Homology) in the AAA Family of ATPases , 1999, The Journal of Biological Chemistry.

[104]  A. Goldberg,et al.  An Archaebacterial ATPase, Homologous to ATPases in the Eukaryotic 26 S Proteasome, Activates Protein Breakdown by 20 S Proteasomes* , 1999, The Journal of Biological Chemistry.

[105]  B. Tomkinson.  Tripeptidyl peptidases: enzymes that count. , 1999, Trends in biochemical sciences.

[106]  C. Crews,et al.  Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[107]  R. Huber,et al.  Proteasome beta-type subunits: unequal roles of propeptides in core particle maturation and a hierarchy of active site function. , 1999, Journal of molecular biology.

[108]  J. Seol,et al.  ATP‐dependent degradation of SulA, a cell division inhibitor, by the HslVU protease in Escherichia coli , 1999, FEBS letters.

[109]  M. Maurizi,et al.  Here's the hook: similar substrate binding sites in the chaperone domains of Clp and Lon. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[110]  M. Hochstrasser,et al.  Eukaryotic 20S proteasome catalytic subunit propeptides prevent active site inactivation by N‐terminal acetylation and promote particle assembly , 1999, The EMBO journal.

[111]  H. Yanagi,et al.  The ATP-Dependent HslVU/ClpQY Protease Participates in Turnover of Cell Division Inhibitor SulA in Escherichia coli , 1999, Journal of bacteriology.

[112]  T. Baker,et al.  Lon and Clp family proteases and chaperones share homologous substrate-recognition domains. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[113]  R. Huber,et al.  Bivalency as a principle for proteasome inhibition. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[114]  M. Ehrmann,et al.  A Temperature-Dependent Switch from Chaperone to Protease in a Widely Conserved Heat Shock Protein , 1999, Cell.

[115]  R. Huber,et al.  Bifunctional inhibitors of the trypsin-like activity of eukaryotic proteasomes. , 1999, Chemistry & biology.

[116]  F. R. Papa,et al.  Interaction of the Doa4 deubiquitinating enzyme with the yeast 26S proteasome. , 1999, Molecular biology of the cell.

[117]  E V Koonin,et al.  AAA+: A class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes. , 1999, Genome research.

[118]  A. Goldberg,et al.  Degradation of cell proteins and the generation of MHC class I-presented peptides. , 1999, Annual review of immunology.

[119]  W. Baumeister,et al.  The 26S proteasome: a molecular machine designed for controlled proteolysis. , 1999, Annual review of biochemistry.

[120]  J. Wang,et al.  Crystal structure determination of Escherichia coli ClpP starting from an EM-derived mask. , 1998, Journal of structural biology.

[121]  W. Baumeister,et al.  The Role of Tricorn Protease and Its Aminopeptidase-Interacting Factors in Cellular Protein Degradation , 1998, Cell.

[122]  W Keilholz,et al.  Cleavage motifs of the yeast 20S proteasome beta subunits deduced from digests of enolase 1. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[123]  Robert Huber,et al.  Contribution of Proteasomal β-Subunits to the Cleavage of Peptide Substrates Analyzed with Yeast Mutants* , 1998, The Journal of Biological Chemistry.

[124]  W. Baumeister,et al.  A Subcomplex of the Proteasome Regulatory Particle Required for Ubiquitin-Conjugate Degradation and Related to the COP9-Signalosome and eIF3 , 1998, Cell.

[125]  A. Brünger,et al.  Structure of the ATP-dependent oligomerization domain of N-ethylmaleimide sensitive factor complexed with ATP , 1998, Nature Structural Biology.

[126]  M. Glickman,et al.  Active site mutants in the six regulatory particle ATPases reveal multiple roles for ATP in the proteasome , 1998, The EMBO journal.

[127]  W. Weis,et al.  Crystal Structure of the Hexamerization Domain of N-ethylmaleimide–Sensitive Fusion Protein , 1998, Cell.

[128]  László Polgár,et al.  Prolyl Oligopeptidase An Unusual β-Propeller Domain Regulates Proteolysis , 1998, Cell.

[129]  T. E. Shrader,et al.  Functional role of the N-terminal region of the Lon protease from Mycobacterium smegmatis. , 1998, Biochemistry.

[130]  R. Huber,et al.  Conformational constraints for protein self-cleavage in the proteasome. , 1998, Journal of molecular biology.

[131]  Sunny Shin,et al.  Substrate binding and sequence preference of the proteasome revealed by active-site-directed affinity probes. , 1998, Chemistry & biology.

[132]  M. Glickman,et al.  Proteasome cerevisiae Saccharomyces The Regulatory Particle of the , 1997 .

[133]  A. Steven,et al.  Enzymatic and Structural Similarities between theEscherichia coli ATP-dependent Proteases, ClpXP and ClpAP* , 1998, The Journal of Biological Chemistry.

[134]  Koreaki Ito,et al.  Polypeptide binding of Escherichia coli FtsH (HflB) , 1998, Molecular microbiology.

[135]  Erica S. Johnson,et al.  Ump1p Is Required for Proper Maturation of the 20S Proteasome and Becomes Its Substrate upon Completion of the Assembly , 1998, Cell.

[136]  L. Dick,et al.  Potent and selective inhibitors of the proteasome: dipeptidyl boronic acids. , 1998, Bioorganic & medicinal chemistry letters.

[137]  M. Maurizi,et al.  Isolation and Characterization of the Phage T4 PinA Protein, an Inhibitor of the ATP-dependent Lon Protease ofEscherichia coli * , 1998, The Journal of Biological Chemistry.

[138]  L. Van Melderen,et al.  PinA Inhibits ATP Hydrolysis and Energy-dependent Protein Degradation by Lon Protease* , 1998, The Journal of Biological Chemistry.

[139]  W. Baumeister,et al.  26S proteasome structure revealed by three-dimensional electron microscopy. , 1998, Journal of structural biology.

[140]  T. Baker,et al.  PDZ-like Domains Mediate Binding Specificity in the Clp/Hsp100 Family of Chaperones and Protease Regulatory Subunits , 1997, Cell.

[141]  C. Hill,et al.  Structure of the proteasome activator REGα (PA28α) , 1997, Nature.

[142]  Patricia C. Babbitt,et al.  Understanding Enzyme Superfamilies , 1997, The Journal of Biological Chemistry.

[143]  H. Yanagi,et al.  Synergistic roles of HslVU and other ATP-dependent proteases in controlling in vivo turnover of sigma32 and abnormal proteins in Escherichia coli , 1997, Journal of bacteriology.

[144]  Jimin Wang,et al.  The Structure of ClpP at 2.3 Å Resolution Suggests a Model for ATP-Dependent Proteolysis , 1997, Cell.

[145]  D. Wolf,et al.  The Active Sites of the Eukaryotic 20 S Proteasome and Their Involvement in Subunit Precursor Processing* , 1997, The Journal of Biological Chemistry.

[146]  M. Pallen,et al.  The HtrA family of serine proteases , 1997, Molecular microbiology.

[147]  M. Khattar.  Overexpression of the hslVU operon suppresses SOS‐mediated inhibition of cell division in Escherichia coli , 1997, FEBS letters.

[148]  A. Goldberg,et al.  Proteolytic Activity of the ATP-dependent Protease HslVU Can Be Uncoupled from ATP Hydrolysis* , 1997, The Journal of Biological Chemistry.

[149]  A. Goldberg,et al.  The heat-shock protein HslVU from Escherichia coli is a protein-activated ATPase as well as an ATP-dependent proteinase. , 1997, European journal of biochemistry.

[150]  M. Hochstrasser,et al.  Identification of the yeast 20S proteasome catalytic centers and subunit interactions required for active-site formation. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[151]  A. Goldberg,et al.  Covalent modification of the active site threonine of proteasomal beta subunits and the Escherichia coli homolog HslV by a new class of inhibitors. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[152]  R. Huber,et al.  Crystal structure of heat shock locus V (HslV) from Escherichia coli. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[153]  F. Dick,et al.  QSR1, an Essential Yeast Gene with a Genetic Relationship to a Subunit of the Mitochondrial Cytochromebc 1 Complex, Codes for a 60 S Ribosomal Subunit Protein* , 1997, The Journal of Biological Chemistry.

[154]  Craig A. Richmond,et al.  Specific Interactions between ATPase Subunits of the 26 S Protease* , 1997, The Journal of Biological Chemistry.

[155]  P. Kloetzel,et al.  Maturation of mammalian 20 S proteasome: purification and characterization of 13 S and 16 S proteasome precursor complexes. , 1997, Journal of molecular biology.

[156]  R. Huber,et al.  Structure of 20S proteasome from yeast at 2.4Å resolution , 1997, Nature.

[157]  S. Gottesman,et al.  Protein quality control: triage by chaperones and proteases. , 1997, Genes & development.

[158]  Wei Xu,et al.  Editing of ubiquitin conjugates by an isopeptidase in the 26S proteasome , 1997, Nature.

[159]  Wolfgang Baumeister,et al.  The ATP-dependent HslVU protease from Escherichia coli is a four-ring structure resembling the proteasome , 1997, Nature Structural Biology.

[160]  Alexei F. Kisselev,et al.  Processive Degradation of Proteins and Other Catalytic Properties of the Proteasome from Thermoplasma acidophilum* , 1997, The Journal of Biological Chemistry.

[161]  K. Satyshur,et al.  Novel Cyclic Biphenyl Ether Peptide β-Strand Mimetics and HIV-Protease Inhibitors , 1997 .

[162]  L. Dick,et al.  Mechanistic Studies on the Inactivation of the Proteasome by Lactacystin in Cultured Cells* , 1997, The Journal of Biological Chemistry.

[163]  L. Cantley,et al.  Recognition of Unique Carboxyl-Terminal Motifs by Distinct PDZ Domains , 1997, Science.

[164]  A C Steven,et al.  Six‐fold rotational symmetry of ClpQ, the E. coli homolog of the 20S proteasome, and its ATP‐dependent activator, ClpY , 1996, FEBS letters.

[165]  P. Kloetzel,et al.  Analysis of mammalian 20S proteasome biogenesis: the maturation of beta‐subunits is an ordered two‐step mechanism involving autocatalysis. , 1996, The EMBO journal.

[166]  C. Georgopoulos,et al.  Identification and characterization of HsIV HsIU (ClpQ ClpY) proteins involved in overall proteolysis of misfolded proteins in Escherichia coli. , 1996, The EMBO journal.

[167]  W. Baumeister,et al.  Tricorn protease (TRI) interacting factor 1 from Thermoplasma acidophilum is a proline iminopeptidase , 1996, FEBS letters.

[168]  W. Baumeister,et al.  Tricorn Protease—The Core of a Modular Proteolytic System , 1996, Science.

[169]  Koreaki Ito,et al.  A protease complex in the Escherichia coli plasma membrane: HflKC (HflA) forms a complex with FtsH (HflB), regulating its proteolytic activity against SecY. , 1996, The EMBO journal.

[170]  R. Sauer,et al.  The DegP and DegQ periplasmic endoproteases of Escherichia coli: specificity for cleavage sites and substrate conformation , 1996, Journal of bacteriology.

[171]  M. Hochstrasser,et al.  Autocatalytic Subunit Processing Couples Active Site Formation in the 20S Proteasome to Completion of Assembly , 1996, Cell.

[172]  P M Kloetzel,et al.  Peptide antigen production by the proteasome: complexity provides efficiency. , 1996, Immunology today.

[173]  R. Liddington,et al.  Crystal structure of a PDZ domain , 1996, Nature.

[174]  W. Baumeister,et al.  Autocatalytic processing of the 20S proteasome , 1996, Nature.

[175]  Hans-Georg Rammensee,et al.  Coordinated Dual Cleavages Induced by the Proteasome Regulator PA28 Lead to Dominant MHC Ligands , 1996, Cell.

[176]  M. S. Lewis,et al.  Effects of pH and Ca2+ on Heterodimer and Heterotetramer Formation by Chromogranin A and Chromogranin B* , 1996, The Journal of Biological Chemistry.

[177]  John H. Lewis,et al.  Crystal Structures of a Complexed and Peptide-Free Membrane Protein–Binding Domain: Molecular Basis of Peptide Recognition by PDZ , 1996, Cell.

[178]  A. Goldberg,et al.  HslV-HslU: A novel ATP-dependent protease complex in Escherichia coli related to the eukaryotic proteasome. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[179]  Hans-Georg Rammensee,et al.  A role for the proteasome regulator PA28α in antigen presentation , 1996, Nature.

[180]  D. Wolf,et al.  Proteasomes: destruction as a programme. , 1996, Trends in biochemical sciences.

[181]  A. Goldberg,et al.  The proteasome subunit, C2, contains an important site for binding of the PA28 (11S) activator. , 1996, European journal of biochemistry.

[182]  M. Rechsteiner,et al.  Proposed Role of a γ-Interferon Inducible Proteasome-Regulator in Antigen Presentation , 1996 .

[183]  Eleanor J. Dodson,et al.  Penicillin acylase has a single-amino-acid catalytic centre , 1996, Nature.

[184]  A. Murzin,et al.  A protein catalytic framework with an N-terminal nucleophile is capable of self-activation , 1995, Nature.

[185]  A. Rivett,et al.  LMP2+ proteasomes are required for the presentation of specific antigens to cytotoxic T lymphocytes , 1995, Current Biology.

[186]  B L Trus,et al.  Homology in structural organization between E. coli ClpAP protease and the eukaryotic 26 S proteasome. , 1995, Journal of molecular biology.

[187]  C. Slaughter,et al.  Primary structures of two homologous subunits of PA28, a γ‐interferon‐inducible protein activator of the 20S proteasome , 1995, FEBS letters.

[188]  M. Hochstrasser,et al.  Biogenesis, structure and function of the yeast 20S proteasome. , 1995, The EMBO journal.

[189]  R F Standaert,et al.  Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin , 1995, Science.

[190]  W Baumeister,et al.  Proteasome from Thermoplasma acidophilum: a threonine protease. , 1995, Science.

[191]  R. Huber,et al.  Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A resolution. , 1995, Science.

[192]  C. Craik,et al.  Structural basis of substrate specificity in the serine proteases , 1995, Protein science : a publication of the Protein Society.

[193]  W. Baumeister,et al.  Proteasome sequences in eubacteria. , 1994, Trends in biochemical sciences.

[194]  K. Rajewsky,et al.  MHC class I expression in mice lacking the proteasome subunit LMP-7. , 1994, Science.

[195]  W. Baumeister,et al.  Existence of a molecular ruler in proteasomes suggested by analysis of degradation products , 1994, FEBS letters.

[196]  M. Orłowski,et al.  Evidence that the nature of amino acid residues in the P3 position directs substrates to distinct catalytic sites of the pituitary multicatalytic proteinase complex (proteasome). , 1994, Biochemistry.

[197]  C. Slaughter,et al.  PA28 activator protein forms regulatory caps on proteasome stacked rings. , 1994, Journal of molecular biology.

[198]  V. Engelhard.  Structure of peptides associated with MHC class I molecules. , 1994, Current opinion in immunology.

[199]  W. Baumeister,et al.  Structural features of the 26 S proteasome complex. , 1993, Journal of molecular biology.

[200]  F. Blattner,et al.  Sequence analysis of four new heat-shock genes constituting the hslTS/ibpAB and hslVU operons in Escherichia coli. , 1993, Gene.

[201]  D. Finley,et al.  MHC-linked LMP gene products specifically alter peptidase activities of the proteasome , 1993, Nature.

[202]  S. Frentzel,et al.  The major‐histocompatibility‐complex‐encoded β‐type proteasome subunits LMP2 and LMP7 , 1993 .

[203]  F. Blattner,et al.  Characterization of twenty-six new heat shock genes of Escherichia coli , 1993, Journal of bacteriology.

[204]  A. Goldberg,et al.  Role of proteasomes in antigen presentation. , 1993, Enzyme & protein.

[205]  J. Monaco,et al.  Biochemical purification of distinct proteasome subsets. , 1993, Enzyme & protein.

[206]  M. McPherson,et al.  Novel thioether bond revealed by a 1.7 Å crystal structure of galactose oxidase , 1994, Nature.

[207]  R Hegerl,et al.  The three‐dimensional structure of proteasomes from Thermoplasma acidophilum as determined by electron microscopy using random conical tilting , 1991, FEBS letters.

[208]  S. Ōmura,et al.  Lactacystin, a novel microbial metabolite, induces neuritogenesis of neuroblastoma cells. , 1991, The Journal of antibiotics.

[209]  C. Georgopoulos,et al.  The HtrA (DegP) protein, essential for Escherichia coli survival at high temperatures, is an endopeptidase , 1990, Journal of bacteriology.

[210]  R. Huber,et al.  The refined 1.9 A crystal structure of human alpha‐thrombin: interaction with D‐Phe‐Pro‐Arg chloromethylketone and significance of the Tyr‐Pro‐Pro‐Trp insertion segment. , 1989, The EMBO journal.

[211]  J. Beckwith,et al.  Characterization of degP, a gene required for proteolysis in the cell envelope and essential for growth of Escherichia coli at high temperature , 1989, Journal of bacteriology.

[212]  A. Varshavsky,et al.  In vivo half-life of a protein is a function of its amino-terminal residue. , 1986, Science.

[213]  H. Reinauer,et al.  Activation of the multicatalytic proteinase from rat skeletal muscle by fatty acids or sodium dodecyl sulphate. , 1985, The Biochemical journal.

[214]  A. Goldberg,et al.  Isolation and characterization of protease do from Escherichia coli, a large serine protease containing multiple subunits. , 1983, Archives of biochemistry and biophysics.

[215]  R. Huber,et al.  Structural basis of the activation and action of trypsin , 1978 .

[216]  J. Harris.  Release of a macromolecular protein component from human erythrocyte ghosts. , 1968, Biochimica et biophysica acta.