Escherichia coli K-12 substr. MG1655 Protein: HslU hexamer

Gene: hslU Accession Numbers: EG11881 (EcoCyc), b3931, ECK3923

Synonyms: clpY, htpI, D48.5

Regulation Summary Diagram

Regulation summary diagram for hslU

Component of: HslVU protease (extended summary available)

Subunit composition of HslU hexamer = [HslU]6
         ATPase component of the HslVU protease = HslU

HslU is the ATPase component of the HslVU protease, which is composed of HslU and HslV [Rohrwild96, Yoo96]. This ATP-stimulated protease exhibits activity similar to that of the chymotrypsin-like activity of the eukaryotic proteasome [Rohrwild96]. HslU also exhibits protein chaperone activity [Seong00].

HslU is required for growth under conditions of elevated temperature [Peruski94, Katayama96a]. HslU is involved in wild-type cell size control under some conditions [Katayama96a]. The relationship between HslU and the cell division inhibitor SulA is complicated; HslVU degrades the Lon substrate SulA [Seong99], whereas HslU also exhibits chaperone activity toward SulA [Seong00]. A similar relationship may exist between HslU and DnaA [Slominska03]. The HslVU protease plays a role in clearing the defective peptides produced in the presence of puromycin [Missiakas96]. HslVU is capable of filling the role of the Lon protease under some conditions [Wu99].

Crystal structures of HslU [Bochtler00] and of the HslVU complex are presented [Bochtler00, Sousa00, Song00, Wang01b, Wang01d, Bochtler01, Wang03, Kwon03]. HslU and HslV form ring shaped complexes [Rohrwild96] of protein hexamers [Kessel96] that stack into a four-ring cylinder with HslU rings on each end and HslV rings in the center [Rohrwild97]. HslU appears to be homodimeric in the absence of ATP and to form a higher-order complex in the presence of ATP [Yoo96]. HslU and HslV coimmunoprecipitate, whereas the association is labile under chromatographic conditions [Rohrwild96]. Interactions among HslU and HslV are discussed in detail [Yoo97, Huang97, Yoo96, Rohrwild97, Song00, Seong02, Lee03, Kwon03, Azim05, Yakamavich08, Lee09c, Sundar10]. The role of ATP binding and hydrolysis in complex formation and activity is discussed [Yoo96, Yoo97a, Shin96, Huang97, Rohrwild96, Yoo96, Seong99, Song00, Wang01c]. Stimulation of HslU-mediated ATP hydrolysis by poly-L-lysine stimulates the peptidase activity of HslV within the HslVU complex [Yoo96a]. The presence of a protein substrate also stimulates HslVU protease activity [Seol97]. The activity of the HslVU complex is discussed in detail [Bogyo97, Huang97, Wang01b].

The crystal structure of a functional hybrid complex of E. coli HslU with Bacillus subtilis HslV (CodW) has also been determined [Wang05a].

An hslU mutant exhibits a defect in growth at high temperature and shows abnormally small cell size under some conditions [Katayama96a]. A K63T mutation in the ATP binding site causes defects in ATPase activity and in HslU multimerization [Shin96]. A C287V mutation causes an ATPase defect but does not eliminate ATP-stimulated HslVU complex formation or protease activity [Yoo98]. A C261V mutation inhibits N-ethylmaleimide-mediated dissociation of HslU complexes [Yoo98]. Overproduction of HslU and HslV causes resistance to nitrofurantoin and to UV irradiation in a lon mutant background [Khattar97]. An hslU mutation causes synthetic lethality with a dnaA204 mutation [Slominska03]. An hslU mutation suppresses the heat sensitivity of a dnaA46 mutant [Katayama96a]. Genetic interactions between hslVU and lon are discussed; Lon functions can be carried out by HslVU [Wu99].

HslU has similarity to ClpX [Gottesman93]. HslU has structural similarity to FtsH [Karata01]. HslU has 52% identity to Bacillus subtilis CodX [Kang01]. HslU has similarity, including an ATP/GTP-binding motif, to a protein from Pasteurella haemolytica [Chuang93a]. HslU has similarity to Leptospira borgpetersenii serovar hardjobovis HslU [Lin01], to Leishmania infantum HslU [Couvreur02], and to a Lactobacillus leichmannii protein [Becker96]. Structural similarity between Lon and Clp proteases is discussed [Smith99]. E. coli HslU exhibits stimulatory activity toward Thermotoga maritima HslV [Song03].

Regulation has been described [Chuang93a, Peruski94, Rohrwild96]. Transcription is induced by heat shock [Chuang93a, Peruski94].

The Arc repressor is an efficient substrate for HslVU and its N-terminus serves as a degradation tag that strongly binds to HslU in an ATP-dependent manner [Burton05]. A conserved GYVG pore motif is involved in the unfolding and translocation of protein substrates into the inner core for degradation by HslV [Park05]. HslUV is a more effective unfoldase when degrading substrates from the N-terminus toward the C-terminus, than in the opposite direction [Koodathingal09].

HslU (ClpY) contains three discrete domains, N, I and C. The I domain contains residues in specific loops that are involved in recognition and interaction with natural protein substrates and their delivery to HslV (ClpQ). The C domain is necessary for association with HslV. The N domain contains highly conserved sequences that contribute to the central pore [Lien09, Hsieh11].

In vivo mutant studies using yeast two-hybrid analysis and pulldown assays identified sites essential for translocation of engaged substrates, and an ATP-binding site in domain N that has separate roles in oligomerization and complex formation with HslV. Tyrosine 408 is critical for HslU hexamer formation [Hsieh11]. Molecular modeling and dynamics simulations have been used to elucidate allosteric mechanisms of substrate unfolding and translocation by HslU [Kravats11].

The hexameric ring formed by HslU binds and unfolds substrates and then translocates them through its axial pore into the HslV degradation chamber. Kinetic analyses of wild-type and mutant HslU have shown that the I domain of HslU has roles in the coordination of substrate binding, ATPase activity, and protein degradation by HslV. The N-terminal residues of an engineered Arc substrate were shown to bind to the axial pore of the HslU hexameric ring mediated by a conserved pore loop. The I domain loops of the hexamer form a cavity leading to the pore where substrate contact occurs [Sundar12].

An F441Y mutation in HslU enhanced HslV peptidase and caseinolytic activity, but partially reduced its ATPase and SulA degradation activity. A P315T mutant had wild-type peptidase activity, but showed enhanced ATPase, caseinolytic and SulA degradation activities. A P315T/F441Y double mutant showed an augmentation of all four activities. The implications of these data for the molecular evolution of HslU were discussed [Sung14].

Reviews: [Schmidt09, Goldberg]

Locations: cytosol, membrane

Map Position: [4,118,439 <- 4,119,770] (88.77 centisomes, 320°)
Length: 1332 bp / 443 aa

Molecular Weight of Polypeptide: 49.594 kD (from nucleotide sequence), 50 kD (experimental) [Yoo96]

Molecular Weight of Multimer: 350 kD (experimental) [Kessel96], 450 kD (experimental) [Yoo96]

Unification Links: ASAP:ABE-0012843, CGSC:34157, DIP:DIP-31855N, DisProt:DP00100, EchoBASE:EB1827, EcoGene:EG11881, EcoliWiki:b3931, ModBase:P0A6H5, OU-Microarray:b3931, PortEco:hslU, PR:PRO_000022934, Pride:P0A6H5, Protein Model Portal:P0A6H5, RefSeq:NP_418366, RegulonDB:EG11881, SMR:P0A6H5, String:511145.b3931, UniProt:P0A6H5

Relationship Links: InterPro:IN-FAMILY:IPR003593, InterPro:IN-FAMILY:IPR003959, InterPro:IN-FAMILY:IPR004491, InterPro:IN-FAMILY:IPR019489, InterPro:IN-FAMILY:IPR027417, Panther:IN-FAMILY:PTHR11262:SF3, PDB:Structure:1DO0, PDB:Structure:1DO2, PDB:Structure:1E94, PDB:Structure:1G4A, PDB:Structure:1G4B, PDB:Structure:1HQY, PDB:Structure:1HT1, PDB:Structure:1HT2, PDB:Structure:1YYF, Pfam:IN-FAMILY:PF00004, Pfam:IN-FAMILY:PF07724, Pfam:IN-FAMILY:PF10431, Smart:IN-FAMILY:SM00382, Smart:IN-FAMILY:SM01086

In Paralogous Gene Group: 221 (2 members)

Gene-Reaction Schematic

Gene-Reaction Schematic

GO Terms:
Biological Process:
Inferred from experimentGO:0009408 - response to heat [Chuang93]
Inferred from experimentInferred by computational analysisGO:0043335 - protein unfolding [GOA06, Park05]
Inferred by computational analysisGO:0006508 - proteolysis [GOA01a]
Molecular Function:
Inferred from experimentGO:0005515 - protein binding [Hsieh11, Lien09, Butland05, Lee03, Wang01c, Wang01b]
Inferred from experimentInferred by computational analysisGO:0005524 - ATP binding [UniProtGOA11a, GOA06, GOA01a, Hsieh11, Yakamavich08]
Inferred from experimentInferred by computational analysisGO:0016887 - ATPase activity [GOA06, GOA01a, Sundar12]
Inferred from experimentGO:0042802 - identical protein binding [Lasserre06, Lee03]
Inferred by computational analysisGO:0000166 - nucleotide binding [UniProtGOA11a]
Inferred by computational analysisGO:0070011 - peptidase activity, acting on L-amino acid peptides [GOA01a]
Cellular Component:
Inferred from experimentInferred by computational analysisGO:0005829 - cytosol [DiazMejia09, Ishihama08, LopezCampistrou05]
Inferred from experimentInferred by computational analysisGO:0009376 - HslUV protease complex [GOA06, GOA01a, Yoo96, Rohrwild96]
Inferred from experimentGO:0016020 - membrane [Lasserre06]
Inferred by computational analysisGO:0005737 - cytoplasm [UniProtGOA11, UniProtGOA11a]

MultiFun Terms: cell processesadaptationstemperature extremes
cell processescell cycle physiology
cell processescell division
information transferprotein relatedchaperoning, repair (refolding)
information transferprotein relatedturnover, degradation
metabolismdegradation of macromoleculesproteins/peptides/glycopeptides
regulationtype of regulationposttranscriptionalproteases, cleavage of compounds

Essentiality data for hslU knockouts:

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enrichedYes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB LennoxYes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerolYes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucoseYes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Last-Curated 04-Aug-2015 by Fulcher C, SRI International

Subunit of: HslVU protease

Synonyms: ClpYQ protease, HslUV protease

Subunit composition of HslVU protease = [(HslU)6]2[(HslV)6]2
         HslU hexamer = (HslU)6 (extended summary available)
                 ATPase component of the HslVU protease = HslU
         HslV hexamer = (HslV)6 (extended summary available)
                 peptidase component of the HslVU protease = HslV

The HslVU protease exhibits ATP-stimulated activity similar to that of the chymotrypsin-like activity of the eukaryotic proteasome [Rohrwild96, RuizGonzalez06].

HslU and HslV form ring shaped complexes [Rohrwild96] of protein hexamers [Kessel96] that stack into a four-ring cylinder with HslU rings on each end and HslV rings in the center [Rohrwild97].

Of the six potential ATP binding sites on an HslU hexamer only three or four molecules of ATP are bound at saturation. ATP binding controls the assembly and activity of the HslVU complex. The binding of a single molecule of ATP to HslU allows it to bind HslV, and binding of additional ATP molecules support substrate recognition and activate ATP hydrolysis which drives substrate unfolding and translocation. This thermodynamic hierarchy ensures efficient function of HslVU [Yakamavich08].

HslV uses its N-terminal threonine as the active site residue. Mutagenesis studies showed that in the HslV dodecamer only approximately six of the twelve active site threonines are necessary to support full catalytic activity and to stabilize the interaction between HslV and HslU [Lee09c].

The HslU hexamer portion of the HslVU complex recognizes and unfolds native protein substrates and then translocates them to the HslV peptidase chamber for degradation. Sequence signals in the substrate are involved in recognition and degradation. A model was proposed that involves tethering of the N- or C-terminus of a substrate to the protease, with the other terminus undergoing translocation and unfolding in the HslU pore [Sundar10].

The HslVU and Lon proteases degrade RNase R in exponential, but not stationary phase cells and tmRNA-SmpB stimulates the process [Liang12]. The F plasmid transfer activator TraJ is degraded by HslVU during extracytoplasmic stress mediated by CpxAR [LauWong08].

HslUV is one of five ATP-dependent proteases in E. coli that are involved in cellular protein quality control. Along with ClpAP, ClpXP, Lon, and FtsH they remove both misfolded and properly folded proteins [Miller13a].

Review: [Sauer04]

Molecular Weight: 820 kD (experimental) [Bochtler00]

Enzymatic reaction of: ATP-dependent HslVU protease

Inferred from experiment

EC Number: 3.4.21.-

a protein + H2O → a peptide + a peptide

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

Sequence Features

Protein sequence of ATPase component of the HslVU protease with features indicated

Feature Class Location Attached Group Citations Comment
Amino-Acid-Sites-That-Bind 18  
Author statement[UniProt15]
UniProt: ATP; via amide nitrogen and carbonyl oxygen.
Nucleotide-Phosphate-Binding-Region 60 -> 65 ATP
Author statement[UniProt15]
UniProt: ATP.
Mutagenesis-Variant 63  
Inferred from experiment[Shin96]
UniProt: Can neither bind nor hydrolyze ATP. Do not form multimers, but stays as monomer.
Mutagenesis-Variant 80  
Inferred from experiment[Song00]
UniProt: Some effect on protease activity.
Mutagenesis-Variant 88  
Inferred from experiment[Song00]
UniProt: Severly reduced protease activity.
Mutagenesis-Variant 91  
Inferred from experiment[Song00]
UniProt: Partial loss of protease activity.
Mutagenesis-Variant 92  
Inferred from experiment[Song00]
UniProt: Partial loss of protease activity.
Mutagenesis-Variant 93  
Inferred from experiment[Song00]
UniProt: Almost no protease or ATP hydrolysis activity.
Mutagenesis-Variant 95  
Inferred from experiment[Song00]
UniProt: Partial loss of protease activity.
Amino-Acid-Sites-That-Bind 256  
Author statement[UniProt15]
UniProt: ATP.
Mutagenesis-Variant 262  
Inferred from experiment[Yoo98]
UniProt: No effect on ATP hydrolysis. Can support HslV-mediated proteolysis at wild-type levels.
Mutagenesis-Variant 266  
Inferred from experiment[Song00]
UniProt: No effect.
Mutagenesis-Variant 286  
Inferred from experiment[Song00]
UniProt: Reduced protease activity.
Mutagenesis-Variant 288  
Inferred from experiment[Yoo98]
UniProt: No ATP hydrolysis activity. Binds ATP with lower affinity than wild-type. Can support HslV-mediated proteolysis to some extent.
Mutagenesis-Variant 312  
Inferred from experiment[Song00]
UniProt: No effect.
Mutagenesis-Variant 321  
Inferred from experiment[Song00]
UniProt: Complete loss of activity.
Amino-Acid-Sites-That-Bind 321  
Author statement[UniProt15]
UniProt: ATP.
Mutagenesis-Variant 325  
Inferred from experiment[Song00]
UniProt: Complete loss of activity. Forms wild-type complexes with HslV and is able to bind ATP.
Mutagenesis-Variant 385  
Inferred from experiment[Song00]
UniProt: No effect.
Mutagenesis-Variant 393  
Inferred from experiment[Song00]
UniProt: Complete loss of activity.
Amino-Acid-Sites-That-Bind 393  
Author statement[UniProt15]
UniProt: ATP.
Mutagenesis-Variant 436  
Author statement[UniProt15]
UniProt: Partial loss of protease activity; when associated with K-437.
Mutagenesis-Variant 437  
Author statement[UniProt15]
UniProt: Partial loss of protease activity; when associated with K-436.

Sequence Pfam Features

Protein sequence of ATPase component of the HslVU protease with features indicated

Feature Class Location Citations Comment
Pfam PF00004 53 -> 107
Inferred by computational analysis[Finn14]
AAA : ATPase family associated with various cellular activities (AAA)
Pfam PF07724 188 -> 329
Inferred by computational analysis[Finn14]
AAA_2 : AAA domain (Cdc48 subfamily)
Pfam PF10431 335 -> 405
Inferred by computational analysis[Finn14]
ClpB_D2-small : C-terminal, D2-small domain, of ClpB protein

Gene Local Context (not to scale -- see Genome Browser for correct scale)

Gene local context diagram

Transcription Unit

Transcription-unit diagram


10/20/97 Gene b3931 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11881; confirmed by SwissProt match.


Azim05: Azim MK, Goehring W, Song HK, Ramachandran R, Bochtler M, Goettig P (2005). "Characterization of the HslU chaperone affinity for HslV protease." Protein Sci 14(5);1357-62. PMID: 15802652

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Becker96: Becker J, Brendel M (1996). "Molecular characterization of the xerC gene of Lactobacillus leichmannii encoding a site-specific recombinase and two adjacent heat shock genes." Curr Microbiol 32(4);232-6. PMID: 8867465

Bochtler00: Bochtler M, Hartmann C, Song HK, Bourenkov GP, Bartunik HD, Huber R (2000). "The structures of HsIU and the ATP-dependent protease HsIU-HsIV." Nature 403(6771);800-5. PMID: 10693812

Bochtler01: Bochtler M, Song HK, Hartmann C, Ramachandran R, Huber R (2001). "The quaternary arrangement of HslU and HslV in a cocrystal: a response to Wang, Yale." J Struct Biol 135(3);281-93. PMID: 11722168

Bogyo97: Bogyo M, McMaster JS, Gaczynska M, Tortorella D, Goldberg AL, Ploegh H (1997). "Covalent modification of the active site threonine of proteasomal beta subunits and the Escherichia coli homolog HslV by a new class of inhibitors." Proc Natl Acad Sci U S A 94(13);6629-34. PMID: 9192616

Burton05: Burton RE, Baker TA, Sauer RT (2005). "Nucleotide-dependent substrate recognition by the AAA+ HslUV protease." Nat Struct Mol Biol 12(3);245-51. PMID: 15696175

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

Chuang93: Chuang SE, Blattner FR (1993). "Characterization of twenty-six new heat shock genes of Escherichia coli." J Bacteriol 175(16);5242-52. PMID: 8349564

Chuang93a: Chuang SE, Burland V, Plunkett G, Daniels DL, Blattner FR (1993). "Sequence analysis of four new heat-shock genes constituting the hslTS/ibpAB and hslVU operons in Escherichia coli." Gene 1993;134(1);1-6. PMID: 8244018

Couvreur02: Couvreur B, Wattiez R, Bollen A, Falmagne P, Le Ray D, Dujardin JC (2002). "Eubacterial HslV and HslU subunits homologs in primordial eukaryotes." Mol Biol Evol 19(12);2110-7. PMID: 12446803

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Finn14: Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, Heger A, Hetherington K, Holm L, Mistry J, Sonnhammer EL, Tate J, Punta M (2014). "Pfam: the protein families database." Nucleic Acids Res 42(Database issue);D222-30. PMID: 24288371

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Goldberg: Goldberg AL, Akopian TN, Kisselev AF, Lee DH, Rohrwild M (1997). "New insights into the mechanisms and importance of the proteasome in intracellular protein degradation." Biol Chem 378(3-4);131-40. PMID: 9165063

Gottesman93: Gottesman S, Clark WP, de Crecy-Lagard V, Maurizi MR (1993). "ClpX, an alternative subunit for the ATP-dependent Clp protease of Escherichia coli. Sequence and in vivo activities." J Biol Chem 1993;268(30);22618-26. PMID: 8226770

Hsieh11: Hsieh FC, Chen CT, Weng YT, Peng SS, Chen YC, Huang LY, Hu HT, Wu YL, Lin NC, Wu WF (2011). "Stepwise activity of ClpY (HslU) mutants in the processive degradation of Escherichia coli ClpYQ (HslUV) protease substrates." J Bacteriol 193(19);5465-76. PMID: 21803990

Huang97: Huang H, Goldberg AL (1997). "Proteolytic activity of the ATP-dependent protease HslVU can be uncoupled from ATP hydrolysis." J Biol Chem 272(34);21364-72. PMID: 9261150

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Kang01: Kang MS, Lim BK, Seong IS, Seol JH, Tanahashi N, Tanaka K, Chung CH (2001). "The ATP-dependent CodWX (HslVU) protease in Bacillus subtilis is an N-terminal serine protease." EMBO J 20(4);734-42. PMID: 11179218

Karata01: Karata K, Verma CS, Wilkinson AJ, Ogura T (2001). "Probing the mechanism of ATP hydrolysis and substrate translocation in the AAA protease FtsH by modelling and mutagenesis." Mol Microbiol 39(4);890-903. PMID: 11251810

Katayama96a: Katayama T, Kubota T, Takata M, Akimitsu N, Sekimizu K (1996). "Disruption of the hslU gene, which encodes an ATPase subunit of the eukaryotic 26S proteasome homolog in Escherichia coli, suppresses the temperature-sensitive dnaA46 mutation." Biochem Biophys Res Commun 229(1);219-24. PMID: 8954109

Kessel96: Kessel M, Wu W, Gottesman S, Kocsis E, Steven AC, Maurizi MR (1996). "Six-fold rotational symmetry of ClpQ, the E. coli homolog of the 20S proteasome, and its ATP-dependent activator, ClpY." FEBS Lett 398(2-3);274-8. PMID: 8977122

Khattar97: Khattar MM (1997). "Overexpression of the hslVU operon suppresses SOS-mediated inhibition of cell division in Escherichia coli." FEBS Lett 414(2);402-4. PMID: 9315728

Koodathingal09: Koodathingal P, Jaffe NE, Kraut DA, Prakash S, Fishbain S, Herman C, Matouschek A (2009). "ATP-dependent proteases differ substantially in their ability to unfold globular proteins." J Biol Chem 284(28);18674-84. PMID: 19383601

Kravats11: Kravats A, Jayasinghe M, Stan G (2011). "Unfolding and translocation pathway of substrate protein controlled by structure in repetitive allosteric cycles of the ClpY ATPase." Proc Natl Acad Sci U S A 108(6);2234-9. PMID: 21266546

Kwon: Kwon AR, Trame CB, McKay DB "Kinetics of protein substrate degradation by HslUV." J Struct Biol 146(1-2);141-7. PMID: 15037245

Kwon03: Kwon AR, Kessler BM, Overkleeft HS, McKay DB (2003). "Structure and reactivity of an asymmetric complex between HslV and I-domain deleted HslU, a prokaryotic homolog of the eukaryotic proteasome." J Mol Biol 330(2);185-95. PMID: 12823960

Lasserre06: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726

LauWong08: Lau-Wong IC, Locke T, Ellison MJ, Raivio TL, Frost LS (2008). "Activation of the Cpx regulon destabilizes the F plasmid transfer activator, TraJ, via the HslVU protease in Escherichia coli." Mol Microbiol 67(3);516-27. PMID: 18069965

Lee03: Lee YY, Chang CF, Kuo CL, Chen MC, Yu CH, Lin PI, Wu WF (2003). "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." J Bacteriol 185(8);2393-401. PMID: 12670962

Lee09c: Lee JW, Park E, Jeong MS, Jeon YJ, Eom SH, Seol JH, Chung CH (2009). "HslVU ATP-dependent protease utilizes maximally six among twelve threonine active sites during proteolysis." J Biol Chem 284(48);33475-84. PMID: 19801685

Liang12: Liang W, Deutscher MP (2012). "Transfer-messenger RNA-SmpB protein regulates ribonuclease R turnover by promoting binding of HslUV and Lon proteases." J Biol Chem 287(40);33472-9. PMID: 22879590

Lien09: Lien HY, Shy RS, Peng SS, Wu YL, Weng YT, Chen HH, Su PC, Ng WF, Chen YC, Chang PY, Wu WF (2009). "Characterization of the Escherichia coli ClpY (HslU) substrate recognition site in the ClpYQ (HslUV) protease using the yeast two-hybrid system." J Bacteriol 191(13);4218-31. PMID: 19395483

Lin01: Lin M, Li Y (2001). "PCR genome walking identifies a genetic locus comprising two heat shock genes (hslV and hslU) from Leptospira borgpetersenii serovar hardjobovis." Curr Microbiol 43(6);452-6. PMID: 11685516

LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532

Miller13a: Miller JM, Lin J, Li T, Lucius AL (2013). "E. coli ClpA catalyzed polypeptide translocation is allosterically controlled by the protease ClpP." J Mol Biol 425(15);2795-812. PMID: 23639359

Missiakas96: Missiakas D, Schwager F, Betton JM, Georgopoulos C, Raina S (1996). "Identification and characterization of HsIV HsIU (ClpQ ClpY) proteins involved in overall proteolysis of misfolded proteins in Escherichia coli." EMBO J 15(24);6899-909. PMID: 9003766

Park05: Park E, Rho YM, Koh OJ, Ahn SW, Seong IS, Song JJ, Bang O, Seol JH, Wang J, Eom SH, Chung CH (2005). "Role of the GYVG pore motif of HslU ATPase in protein unfolding and translocation for degradation by HslV peptidase." J Biol Chem 280(24);22892-8. PMID: 15849200

Peruski94: Peruski LF, Neidhardt FC (1994). "Identification of a conditionally essential heat shock protein in Escherichia coli." Biochim Biophys Acta 1207(2);165-72. PMID: 8075150

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Other References Related to Gene Regulation

Lien09a: Lien HY, Yu CH, Liou CM, Wu WF (2009). "Regulation of clpQY (hslVU) Gene Expression in Escherichia coli." Open Microbiol J 3;29-39. PMID: 19440251

Nonaka06: Nonaka G, Blankschien M, Herman C, Gross CA, Rhodius VA (2006). "Regulon and promoter analysis of the E. coli heat-shock factor, sigma32, reveals a multifaceted cellular response to heat stress." Genes Dev 20(13);1776-89. PMID: 16818608

Wade06: Wade JT, Roa DC, Grainger DC, Hurd D, Busby SJ, Struhl K, Nudler E (2006). "Extensive functional overlap between sigma factors in Escherichia coli." Nat Struct Mol Biol 13(9);806-14. PMID: 16892065

Wagner09: Wagner MA, Zahrl D, Rieser G, Koraimann G (2009). "Growth phase- and cell division-dependent activation and inactivation of the {sigma}32 regulon in Escherichia coli." J Bacteriol 191(5);1695-702. PMID: 19114495

Zahrl06: Zahrl D, Wagner M, Bischof K, Koraimann G (2006). "Expression and assembly of a functional type IV secretion system elicit extracytoplasmic and cytoplasmic stress responses in Escherichia coli." J Bacteriol 188(18);6611-21. PMID: 16952953

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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