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Escherichia coli K-12 substr. MG1655 Protein: ClpX ATP-dependent protease specificity component and chaperone



Gene: clpX Accession Numbers: EG10159 (EcoCyc), b0438, ECK0432

Synonyms: lopC

Regulation Summary Diagram: ?

Component of:
ClpAXP (summary available)
ClpXP (extended summary available)

Subunit composition of ClpX ATP-dependent protease specificity component and chaperone = [ClpX]6

Summary:
ClpX is an ATP-dependent molecular chaperone that serves as a substrate-specifying adaptor for the ClpP serine protease in the ClpXP and ClpAXP protease complexes. ClpX is a member of the AAA+ (ATPases associated with diverse cellular activities) family of ATPases [Neuwald99, Kimura01]

ClpX protects the lambda O protein from heat-induced aggregation, disassembles lambda aggregates and enhances lambda DNA binding. ATP binding is required for all these effects, and disaggregation requires ATP hydrolysis [Wawrzynow95]. ClpX also converts inactive, dimeric TrfA into its monomeric form (capable of initiating replication of plasmid RK2) in an ATP-dependent manner [Konieczny97].

ClpX is required for normal replication of Mu transposase [MhammediAlaoui94]. ClpX catalyzes the ATP-dependent release of MuA from its active transposase tetramer form, allowing recruitment of host factors necessary for post-recombination steps in Mu transposition [Levchenko95, Kruklitis96]. ClpX is also able to globally unfold MuA monomers. ClpX recognizes a ten amino acid peptide from the carboxy-terminus of MuA when it is revealed by MuB. ClpX will recognize other proteins with this tag artificially attached [Levchenko97].

Each ClpX monomer has two PDZ domains that bind to the carboxy-terminus of target proteins. These domains show up as disordered sequence in NMR and are unstable when expressed independently [Levchenko97a, Smith99]. ClpX also has an ATP-binding site motif and a zinc-binding domain, the latter being a member of the treble clef zinc finger family, involved in macromolecular interactions [Gottesman93, Donaldson03].

ClpX recognises C-terminal residues 9-11 of the ssrA peptide tag (AANDENYALAA) [Flynn01]. Mutations in the central pore of the ClpX hexamer disrupt recognition of ssrA-tag containing substrates [Siddiqui04, Farrell07]. The ssrA-tag interacts with pore loop regions located in the central core of the ClpX hexamer [Martin08, Martin08a].

ClpX is a hexamer of ClpX monomers, stabilized by ATP binding and capable of capping ClpP tetradecamers [Grimaud98]. While the ClpX ATP-binding site is necessary for oligomerization and binding to ClpP, both processes continue in the absence of ATP [Banecki01]. ATP-bound ClpX is protease resistant [Singh01]. The carboxy-terminus of ClpX is required for interaction with ClpP, as is the tripeptide IGF, though the latter is dispensible for ClpX chaperone activities [Kim01, Singh01]. Mutations in the interface between the carboxy-terminus of each subunit and the ATPase domain of its neighbor prevent disassembly of bound substrate [Joshi03]. Packing of the the small AAA domain (residues 3199-424) against a neigbouring large AAA domain (residues 65-314) forms the major interface between ClpA subunits [Glynn09, Glynn12].

Functional ClpX is an asymmetric hexamer - ClpX subunits bind nucleotide with differing affinity and at least two ClpX subunits do not bind nucleotide [Hersch05]. ClpX forms an asymmetric hexamer containing two types of subunits: nucleotide free (termed U for unloaded) or containing bound nucleotide (termed L for loaded). The subunits are arranged in an L/U/L/L/U/L pattern [Glynn09]. L and U subunits switch dynamically during the ClpX cycle; disulfide cross-links which block L → U switching uncouple ATP hydrolysis from substrate unfolding and translocation in vitro [Stinson13].

SspB binding stimulates ClpX ATPase activity [Wah02].

ClpX is required for adaptation to and extended viability in stationary phase, as well as growth in SDS [Weichart03, Rajagopal02].

ClpX can be expressed without ClpP [Yoo94].

Reviews: [Burton05, Zolkiewski06]
Comments: [Inobe08]

Citations: [Thibault06, Thibault12, Thibault06a, Wojtyra03]

Gene Citations: [Li00, Rhodius05]

Locations: cytosol

Map Position: [456,650 -> 457,924] (9.84 centisomes)
Length: 1275 bp / 424 aa

Molecular Weight of Polypeptide: 46.356 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0001517 , CGSC:31287 , DIP:DIP-35907N , EchoBASE:EB0157 , EcoGene:EG10159 , EcoliWiki:b0438 , ModBase:P0A6H1 , OU-Microarray:b0438 , PortEco:clpX , PR:PRO_000022300 , Pride:P0A6H1 , Protein Model Portal:P0A6H1 , RefSeq:NP_414972 , RegulonDB:EG10159 , SMR:P0A6H1 , String:511145.b0438 , Swiss-Model:P0A6H1 , UniProt:P0A6H1

Relationship Links: InterPro:IN-FAMILY:IPR003593 , InterPro:IN-FAMILY:IPR004487 , InterPro:IN-FAMILY:IPR010603 , InterPro:IN-FAMILY:IPR013093 , InterPro:IN-FAMILY:IPR019489 , InterPro:IN-FAMILY:IPR027417 , Panther:IN-FAMILY:PTHR11262:SF4 , PDB:Structure:1OVX , PDB:Structure:2DS5 , PDB:Structure:2DS6 , PDB:Structure:2DS7 , PDB:Structure:2DS8 , PDB:Structure:3HTE , PDB:Structure:3HWS , PDB:Structure:4I4L , PDB:Structure:4I5O , PDB:Structure:4I9K , PDB:Structure:4I34 , PDB:Structure:4I63 , PDB:Structure:4I81 , Pfam:IN-FAMILY:PF06689 , Pfam:IN-FAMILY:PF07724 , Pfam:IN-FAMILY:PF10431 , Smart:IN-FAMILY:SM00382 , Smart:IN-FAMILY:SM00994 , Smart:IN-FAMILY:SM01086

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0006200 - ATP catabolic process Inferred from experiment [Wojtkowiak93]
GO:0006508 - proteolysis Inferred from experiment [Wojtkowiak93]
GO:0051301 - cell division Inferred from experiment [Camberg11]
GO:0006457 - protein folding Inferred by computational analysis [GOA06, GOA01a]
GO:0006950 - response to stress Inferred by computational analysis [UniProtGOA11a]
GO:0016032 - viral process Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0004176 - ATP-dependent peptidase activity Inferred from experiment [Wojtkowiak93]
GO:0005524 - ATP binding Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA06, GOA01a, Grimaud98]
GO:0042802 - identical protein binding Inferred from experiment [Rajagopala14, Stinson13, Glynn09]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11a]
GO:0008270 - zinc ion binding Inferred by computational analysis [GOA01a]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
GO:0046983 - protein dimerization activity Inferred by computational analysis [GOA01a]
GO:0051082 - unfolded protein binding Inferred by computational analysis [GOA06, GOA01a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, LopezCampistrou05]

MultiFun Terms: information transfer protein related chaperoning, repair (refolding)
information transfer protein related turnover, degradation
metabolism degradation of macromolecules proteins/peptides/glycopeptides

Essentiality data for clpX knockouts: ?

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

Credits:
Curated 13-Jan-2006 by Shearer A , SRI International
Revised 25-May-2011 by Brito D
Last-Curated ? 06-Aug-2013 by Mackie A , Macquarie University


Subunit of: ClpAXP

Synonyms: ATP-dependent endopeptidase Clp, ATP-dependent protease Clp

Subunit composition of ClpAXP = [(ClpP)14][(ClpA)6][(ClpX)6]
         ClpP serine protease = (ClpP)14 (extended summary available)
         ClpA ATP-dependent protease specificity component and chaperone = (ClpA)6
         ClpX ATP-dependent protease specificity component and chaperone = (ClpX)6 (extended summary available)

Summary:
Hybrid complexes can form in vitro, consisting of a ClpP tetradecamer capped at one end with ClpA and at the other with ClpX. These complexes are translocation competent. Stoichiometry in vivo suggests heterocomplexes may form there, as well [Ortega04].


Enzymatic reaction of: ATP-dependent Clp protease (ClpAXP)

Synonyms: ATP-binding Clp protease, ATP-dependent Clp endopeptidase

EC Number: 3.4.21.92

a protein + H2O <=> a peptide + a peptide

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.


Subunit of: ClpXP

Subunit composition of ClpXP = [(ClpP)14][(ClpX)6]2
         ClpP serine protease = (ClpP)14 (extended summary available)
         ClpX ATP-dependent protease specificity component and chaperone = (ClpX)6 (extended summary available)

Summary:
ClpXP is a serine protease complex responsible for the ATP-dependent degradation of a wide range of proteins [Gottesman93, Wojtkowiak93].

ClpXP degrades the altered Mu immunity repressor, Vir. When Vir is present, the normal immunity repressor, Rep, becomes more vulnerable to ClpXP-mediated degradation as well [Welty97]. ClpXP can also degrade MuA, although it does not degrade it all, allowing ClpX to act in its chaperone capacity to assist MuA function [Jones98, MhammediAlaoui94].

ClpXP is partially responsible for degradation of proteins with the SsrA degradation tag, including SsrA-tagged lambda repressor [Bohn02, Gottesman98]. ClpXP degrades stably folded SsrA proteins efficiently, but only poorly degrades proteins bearing SsrA tags artificially attached in the middle of their sequences via cysteine linkages [Kenniston04].

ClpXP can degrade DNA-bound lambda O protein when transcription is possible, otherwise, it is stable [Zylicz98]. ClpXP-mediated degradation of lambda O protein can affect the lysis/lysogeny decision under certain growth conditions [Wojtkowiak93, Czyz01].

ClpXP is also required for degradation of the starvation-induced proteins Dps and sigma S during exponential growth [Stephani03, Schweder96].

Several other ClpXP substrates have been discovered. ClpXP degrades variants of the restriction enzyme EcoKI that have impaired enzymatic function, the mutagenically active protein UmuD' when it is in a heterodimer with unmodified UmuD and the antitoxin Phd from the Doc-Phd toxin/antitoxin pair (from plasmid prophage P1) [ONeill01, Frank96, Lehnherr95].

Putative ClpXP substrates were found by trapping with inactivated ClpP. Potential substrates included some with SsrA-like tails (crl, dksA, fnr, iscR, rplJ, rplU, gcp, pepB, katE, nrdH, tpx, chew, cysA, exbB, acnB, aldA, glpD, glyA, IldD and ycbW), MuA-like carboxy-terminal motifs (paaA, pncB, ribB, ybaQ), novel amino-terminal binding motifs (crl, dksA, fnr, lexA, rpoS, rplE, rplJ, rplK, rplS, rplU, tufB, dps, katE, nrdH, tpx, insH, chew, cysA, gatA, ompA, secA, aceA, atpD, cysD, dada, fabB, gapA, gatY, gatZ, glcB, glyA, iscS, lipA, moaA, pncB, tnaA, udp, ybaQ and ycbW) and no specific binding motifs (rseA, rplN, lon, clpX, dnaK, groEL, ftsZ, iscU, yebO and ygaT) [Flynn03].

SspB binds to SsrA-tagged proteins via its amino-terminal domain and enhances their degradation by ClpXP through carboxy-terminal binding to ClpXP [Levchenko00, Wah03]. SspB alone is sufficient to allow interaction with ClpXP. A protein that has been covalently linked to SspB becomes a ClpXP substrate even in the absence of an SsrA tag [Bolon04]. ClpX and SspB bind to overlapping parts of the SsrA tag, weakening the direct SsrA-ClpX interaction. The SspB-ClpX interaction overcomes this weakening effect [Hersch04]. Trapping experiments based on SspB show that RseA, which is cleaved from the membrane and binds to sigma E as an inhibitor during stress interacts with SspB and is degraded by ClpXP, thus releasing sigma E [Flynn04]. Sigma S degradation by ClpXP requires the adaptor RssB, which binds to Region 2.5 of sigma S, allowing binding of ClpX at the amino-terminus and subsequent degradation by ClpXP [Muffler96, Zhou01, Studemann03]. Each ClpX hexamer has three SspB binding domains to match up with two ClpXP binding domains per SspB dimer, so only one SspB dimer can function with a given ClpX hexamer at a time [Bolon04a]. UmuD operates in a manner similar to SspB, binding to the ClpX amino-terminus and serving as a substrate tether for UmuD' [Neher03].

ClpXP consists of a ClpP tetradecamer capped at one or both ends by ClpX hexamers [Grimaud98].

Substrates bind to the distal surface of ClpX, and then are passed off to the inner cavity of ClpP to be degraded, in a process that is driven by ATP and modulated by ClpXP protease specificity-enhancing factor [Ortega00, Thibault06a]. This process involves both static and dynamic contacts between ClpX and ClpP [Martin07]. The initial ClpX-mediated denaturation of substrate is the rate-limiting step in degradation of a well-folded protein, such as SsrA-tagged GFP [Kim00b]. ClpXP uses mechanical force to unfold its protein substrate. Substrate translocation occurs in phases - a dwell phase when there is no movement followed by a burst phase during which ClpXP almost instantaneously translocates a portion of the substrate [Maillard11, AubinTam11, Sen13].

ClpXP is required for limitation of lambda phage early DNA replication during slow growth [Wegrzyn].

ClpXP is required for acquisition of the genes encoding the restriction enzymes EcoKI and EcoAI by conjugation or transformation [Makovets98].

Despite lambda O initiator protein being a ClpXP substrate, lambda replication does not depend on ClpXP levels [Szalewska94].

Reviews: [Baker12]
Comments: [AlegreCebollada11, Maurizi13]

Credits:
Last-Curated ? 09-Jan-2006 by Shearer A , SRI International


Enzymatic reaction of: protease (ClpXP)

EC Number: 3.4.21.92

a protein + H2O <=> a peptide + a peptide

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.


Sequence Features

Feature Class Location Common Name Citations Comment
Cleavage-of-Initial-Methionine 1  
[Wojtkowiak93, UniProt11]
UniProt: Removed.
Chain 2 -> 424  
[UniProt09]
UniProt: ATP-dependent Clp protease ATP-binding subunit clpX;
Zn-Finger-Region 15 -> 40  
[UniProt10]
UniProt: C4-type;
Protein-Segment 65 -> 314 large AAA+ domain
[Glynn12]
 
Nucleotide-Phosphate-Binding-Region 119 -> 126  
[UniProt10a]
UniProt: ATP; Non-Experimental Qualifier: potential;
Sequence-Conflict 268 -> 274  
[Yoo93, UniProt10]
Alternate sequence: IGFGATV → HWCWRSG; UniProt: (in Ref. 2; CAA80816);
Protein-Segment 315 -> 318 hinge region
[Glynn12]
 
Protein-Segment 319 -> 424 small AAA+ domain
[Glynn12]
 


Gene Local Context (not to scale): ?

Transcription Units:

Notes:

History:
10/20/97 Gene b0438 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10159; confirmed by SwissProt match.


References

AlegreCebollada11: Alegre-Cebollada J, Kosuri P, Fernandez JM (2011). "Protease power strokes force proteins to unfold." Cell 145(3);339-40. PMID: 21529709

AubinTam11: Aubin-Tam ME, Olivares AO, Sauer RT, Baker TA, Lang MJ (2011). "Single-molecule protein unfolding and translocation by an ATP-fueled proteolytic machine." Cell 145(2);257-67. PMID: 21496645

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

Baker12: Baker TA, Sauer RT (2012). "ClpXP, an ATP-powered unfolding and protein-degradation machine." Biochim Biophys Acta 1823(1);15-28. PMID: 21736903

Banecki01: Banecki B, Wawrzynow A, Puzewicz J, Georgopoulos C, Zylicz M (2001). "Structure-function analysis of the zinc-binding region of the Clpx molecular chaperone." J Biol Chem 276(22);18843-8. PMID: 11278349

Bohn02: Bohn C, Binet E, Bouloc P (2002). "Screening for stabilization of proteins with a trans-translation signature in Escherichia coli selects for inactivation of the ClpXP protease." Mol Genet Genomics 266(5);827-31. PMID: 11810257

Bolon04: Bolon DN, Grant RA, Baker TA, Sauer RT (2004). "Nucleotide-dependent substrate handoff from the SspB adaptor to the AAA+ ClpXP protease." Mol Cell 16(3);343-50. PMID: 15525508

Bolon04a: Bolon DN, Wah DA, Hersch GL, Baker TA, Sauer RT (2004). "Bivalent tethering of SspB to ClpXP is required for efficient substrate delivery: a protein-design study." Mol Cell 13(3);443-9. PMID: 14967151

Burton05: Burton BM, Baker TA (2005). "Remodeling protein complexes: insights from the AAA+ unfoldase ClpX and Mu transposase." Protein Sci 14(8);1945-54. PMID: 16046622

Camberg11: Camberg JL, Hoskins JR, Wickner S (2011). "The interplay of ClpXP with the cell division machinery in Escherichia coli." J Bacteriol 193(8);1911-8. PMID: 21317324

Czyz01: Czyz A, Zielke R, Wegrzyn G (2001). "Rapid degradation of bacteriophage lambda O protein by ClpP/ClpX protease influences the lysis-versus-lysogenization decision of the phage under certain growth conditions of the host cells." Arch Virol 146(8);1487-98. PMID: 11676412

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

Donaldson03: Donaldson LW, Wojtyra U, Houry WA (2003). "Solution structure of the dimeric zinc binding domain of the chaperone ClpX." J Biol Chem 278(49);48991-6. PMID: 14525985

Farrell07: Farrell CM, Baker TA, Sauer RT (2007). "Altered specificity of a AAA+ protease." Mol Cell 25(1);161-6. PMID: 17218279

Flynn01: Flynn JM, Levchenko I, Seidel M, Wickner SH, Sauer RT, Baker TA (2001). "Overlapping recognition determinants within the ssrA degradation tag allow modulation of proteolysis." Proc Natl Acad Sci U S A 98(19);10584-9. PMID: 11535833

Flynn03: Flynn JM, Neher SB, Kim YI, Sauer RT, Baker TA (2003). "Proteomic discovery of cellular substrates of the ClpXP protease reveals five classes of ClpX-recognition signals." Mol Cell 11(3);671-83. PMID: 12667450

Flynn04: Flynn JM, Levchenko I, Sauer RT, Baker TA (2004). "Modulating substrate choice: the SspB adaptor delivers a regulator of the extracytoplasmic-stress response to the AAA+ protease ClpXP for degradation." Genes Dev 18(18);2292-301. PMID: 15371343

Frank96: Frank EG, Ennis DG, Gonzalez M, Levine AS, Woodgate R (1996). "Regulation of SOS mutagenesis by proteolysis." Proc Natl Acad Sci U S A 93(19);10291-6. PMID: 8816793

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

Glynn09: Glynn SE, Martin A, Nager AR, Baker TA, Sauer RT (2009). "Structures of asymmetric ClpX hexamers reveal nucleotide-dependent motions in a AAA+ protein-unfolding machine." Cell 139(4);744-56. PMID: 19914167

Glynn12: Glynn SE, Nager AR, Baker TA, Sauer RT (2012). "Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine." Nat Struct Mol Biol 19(6);616-22. PMID: 22562135

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."

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

Gottesman98: Gottesman S, Roche E, Zhou Y, Sauer RT (1998). "The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system." Genes Dev 12(9);1338-47. PMID: 9573050

Grimaud98: Grimaud R, Kessel M, Beuron F, Steven AC, Maurizi MR (1998). "Enzymatic and structural similarities between the Escherichia coli ATP-dependent proteases, ClpXP and ClpAP." J Biol Chem 273(20);12476-81. PMID: 9575205

Hersch04: Hersch GL, Baker TA, Sauer RT (2004). "SspB delivery of substrates for ClpXP proteolysis probed by the design of improved degradation tags." Proc Natl Acad Sci U S A 101(33);12136-41. PMID: 15297609

Hersch05: Hersch GL, Burton RE, Bolon DN, Baker TA, Sauer RT (2005). "Asymmetric interactions of ATP with the AAA+ ClpX6 unfoldase: allosteric control of a protein machine." Cell 121(7);1017-27. PMID: 15989952

Inobe08: Inobe T, Kraut DA, Matouschek A (2008). "How to pick a protein and pull at it." Nat Struct Mol Biol 15(11);1135-6. PMID: 18985068

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

Jones98: Jones JM, Welty DJ, Nakai H (1998). "Versatile action of Escherichia coli ClpXP as protease or molecular chaperone for bacteriophage Mu transposition." J Biol Chem 273(1);459-65. PMID: 9417104

Joshi03: Joshi SA, Baker TA, Sauer RT (2003). "C-terminal domain mutations in ClpX uncouple substrate binding from an engagement step required for unfolding." Mol Microbiol 48(1);67-76. PMID: 12657045

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

Kenniston04: Kenniston JA, Burton RE, Siddiqui SM, Baker TA, Sauer RT "Effects of local protein stability and the geometric position of the substrate degradation tag on the efficiency of ClpXP denaturation and degradation." J Struct Biol 146(1-2) 2004;130-40. PMID: 15037244

Kim00b: Kim YI, Burton RE, Burton BM, Sauer RT, Baker TA (2000). "Dynamics of substrate denaturation and translocation by the ClpXP degradation machine." Mol Cell 5(4);639-48. PMID: 10882100

Kim01: Kim YI, Levchenko I, Fraczkowska K, Woodruff RV, Sauer RT, Baker TA (2001). "Molecular determinants of complex formation between Clp/Hsp100 ATPases and the ClpP peptidase." Nat Struct Biol 8(3);230-3. PMID: 11224567

Kimura01: Kimura M, Yoshizumi T, Manabe K, Yamamoto YY, Matsui M (2001). "Arabidopsis transcriptional regulation by light stress via hydrogen peroxide-dependent and -independent pathways." Genes Cells 6(7);607-17. PMID: 11473579

Konieczny97: Konieczny I, Helinski DR (1997). "The replication initiation protein of the broad-host-range plasmid RK2 is activated by the ClpX chaperone." Proc Natl Acad Sci U S A 94(26);14378-82. PMID: 9405620

Kruklitis96: Kruklitis R, Welty DJ, Nakai H (1996). "ClpX protein of Escherichia coli activates bacteriophage Mu transposase in the strand transfer complex for initiation of Mu DNA synthesis." EMBO J 15(4);935-44. PMID: 8631314

Lehnherr95: Lehnherr H, Yarmolinsky MB (1995). "Addiction protein Phd of plasmid prophage P1 is a substrate of the ClpXP serine protease of Escherichia coli." Proc Natl Acad Sci U S A 92(8);3274-7. PMID: 7724551

Levchenko00: Levchenko I, Seidel M, Sauer RT, Baker TA (2000). "A specificity-enhancing factor for the ClpXP degradation machine." Science 289(5488);2354-6. PMID: 11009422

Levchenko95: Levchenko I, Luo L, Baker TA (1995). "Disassembly of the Mu transposase tetramer by the ClpX chaperone." Genes Dev 9(19);2399-408. PMID: 7557391

Levchenko97: Levchenko I, Yamauchi M, Baker TA (1997). "ClpX and MuB interact with overlapping regions of Mu transposase: implications for control of the transposition pathway." Genes Dev 11(12);1561-72. PMID: 9203582

Levchenko97a: Levchenko I, Smith CK, Walsh NP, Sauer RT, Baker TA (1997). "PDZ-like domains mediate binding specificity in the Clp/Hsp100 family of chaperones and protease regulatory subunits." Cell 91(7);939-47. PMID: 9428517

Li00: Li C, Tao YP, Simon LD (2000). "Expression of different-size transcripts from the clpP-clpX operon of Escherichia coli during carbon deprivation." J Bacteriol 182(23);6630-7. PMID: 11073905

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

Maillard11: Maillard RA, Chistol G, Sen M, Righini M, Tan J, Kaiser CM, Hodges C, Martin A, Bustamante C (2011). "ClpX(P) generates mechanical force to unfold and translocate its protein substrates." Cell 145(3);459-69. PMID: 21529717

Makovets98: Makovets S, Titheradge AJ, Murray NE (1998). "ClpX and ClpP are essential for the efficient acquisition of genes specifying type IA and IB restriction systems." Mol Microbiol 28(1);25-35. PMID: 9593294

Martin07: Martin A, Baker TA, Sauer RT (2007). "Distinct static and dynamic interactions control ATPase-peptidase communication in a AAA+ protease." Mol Cell 27(1);41-52. PMID: 17612489

Martin08: Martin A, Baker TA, Sauer RT (2008). "Diverse pore loops of the AAA+ ClpX machine mediate unassisted and adaptor-dependent recognition of ssrA-tagged substrates." Mol Cell 29(4);441-50. PMID: 18313382

Martin08a: Martin A, Baker TA, Sauer RT (2008). "Pore loops of the AAA+ ClpX machine grip substrates to drive translocation and unfolding." Nat Struct Mol Biol 15(11);1147-51. PMID: 18931677

Maurizi13: Maurizi MR, Stan G (2013). "ClpX Shifts into High Gear to Unfold Stable Proteins." Cell 155(3);502-4. PMID: 24243009

MhammediAlaoui94: Mhammedi-Alaoui A, Pato M, Gama MJ, Toussaint A (1994). "A new component of bacteriophage Mu replicative transposition machinery: the Escherichia coli ClpX protein." Mol Microbiol 11(6);1109-16. PMID: 8022280

Muffler96: Muffler A, Fischer D, Altuvia S, Storz G, Hengge-Aronis R (1996). "The response regulator RssB controls stability of the sigma(S) subunit of RNA polymerase in Escherichia coli." EMBO J 15(6);1333-9. PMID: 8635466

Neher03: Neher SB, Sauer RT, Baker TA (2003). "Distinct peptide signals in the UmuD and UmuD' subunits of UmuD/D' mediate tethering and substrate processing by the ClpXP protease." Proc Natl Acad Sci U S A 100(23);13219-24. PMID: 14595014

Neuwald99: Neuwald AF, Aravind L, Spouge JL, Koonin EV (1999). "AAA+: A class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes." Genome Res 9(1);27-43. PMID: 9927482

ONeill01: O'Neill M, Powell LM, Murray NE (2001). "Target recognition by EcoKI: the recognition domain is robust and restriction-deficiency commonly results from the proteolytic control of enzyme activity." J Mol Biol 307(3);951-63. PMID: 11273713

Ortega00: Ortega J, Singh SK, Ishikawa T, Maurizi MR, Steven AC (2000). "Visualization of substrate binding and translocation by the ATP-dependent protease, ClpXP." Mol Cell 6(6);1515-21. PMID: 11163224

Ortega04: Ortega J, Lee HS, Maurizi MR, Steven AC (2004). "ClpA and ClpX ATPases bind simultaneously to opposite ends of ClpP peptidase to form active hybrid complexes." J Struct Biol 146(1-2);217-26. PMID: 15037252

Rajagopal02: Rajagopal S, Sudarsan N, Nickerson KW (2002). "Sodium dodecyl sulfate hypersensitivity of clpP and clpB mutants of Escherichia coli." Appl Environ Microbiol 68(8);4117-21. PMID: 12147516

Rajagopala14: Rajagopala SV, Sikorski P, Kumar A, Mosca R, Vlasblom J, Arnold R, Franca-Koh J, Pakala SB, Phanse S, Ceol A, Hauser R, Siszler G, Wuchty S, Emili A, Babu M, Aloy P, Pieper R, Uetz P (2014). "The binary protein-protein interaction landscape of Escherichia coli." Nat Biotechnol 32(3);285-90. PMID: 24561554

Rhodius05: Rhodius VA, Suh WC, Nonaka G, West J, Gross CA (2005). "Conserved and variable functions of the sigmaE stress response in related genomes." PLoS Biol 4(1);e2. PMID: 16336047

Schweder96: Schweder T, Lee KH, Lomovskaya O, Matin A (1996). "Regulation of Escherichia coli starvation sigma factor (sigma s) by ClpXP protease." J Bacteriol 178(2);470-6. PMID: 8550468

Sen13: Sen M, Maillard RA, Nyquist K, Rodriguez-Aliaga P, Presse S, Martin A, Bustamante C (2013). "The ClpXP Protease Unfolds Substrates Using a Constant Rate of Pulling but Different Gears." Cell 155(3);636-46. PMID: 24243020

Siddiqui04: Siddiqui SM, Sauer RT, Baker TA (2004). "Role of the processing pore of the ClpX AAA+ ATPase in the recognition and engagement of specific protein substrates." Genes Dev 18(4);369-74. PMID: 15004005

Singh01: Singh SK, Rozycki J, Ortega J, Ishikawa T, Lo J, Steven AC, Maurizi MR (2001). "Functional domains of the ClpA and ClpX molecular chaperones identified by limited proteolysis and deletion analysis." J Biol Chem 276(31);29420-9. PMID: 11346657

Smith99: Smith CK, Baker TA, Sauer RT (1999). "Lon and Clp family proteases and chaperones share homologous substrate-recognition domains." Proc Natl Acad Sci U S A 96(12);6678-82. PMID: 10359771

Stephani03: Stephani K, Weichart D, Hengge R (2003). "Dynamic control of Dps protein levels by ClpXP and ClpAP proteases in Escherichia coli." Mol Microbiol 49(6);1605-14. PMID: 12950924

Stinson13: Stinson BM, Nager AR, Glynn SE, Schmitz KR, Baker TA, Sauer RT (2013). "Nucleotide binding and conformational switching in the hexameric ring of a AAA+ machine." Cell 153(3);628-39. PMID: 23622246

Studemann03: Studemann A, Noirclerc-Savoye M, Klauck E, Becker G, Schneider D, Hengge R (2003). "Sequential recognition of two distinct sites in sigma(S) by the proteolytic targeting factor RssB and ClpX." EMBO J 22(16);4111-20. PMID: 12912910

Szalewska94: Szalewska A, Wegrzyn G, Taylor K (1994). "Neither absence nor excess of lambda O initiator-digesting ClpXP protease affects lambda plasmid or phage replication in Escherichia coli." Mol Microbiol 13(3);469-74. PMID: 7997163

Thibault06: Thibault G, Yudin J, Wong P, Tsitrin V, Sprangers R, Zhao R, Houry WA (2006). "Specificity in substrate and cofactor recognition by the N-terminal domain of the chaperone ClpX." Proc Natl Acad Sci U S A 103(47);17724-9. PMID: 17090685

Thibault06a: Thibault G, Tsitrin Y, Davidson T, Gribun A, Houry WA (2006). "Large nucleotide-dependent movement of the N-terminal domain of the ClpX chaperone." EMBO J 25(14);3367-76. PMID: 16810315

Thibault12: Thibault G, Houry WA (2012). "Role of the N-terminal domain of the chaperone ClpX in the recognition and degradation of lambda phage protein O." J Phys Chem B 116(23);6717-24. PMID: 22360725

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Wah02: Wah DA, Levchenko I, Baker TA, Sauer RT (2002). "Characterization of a Specificity Factor for an AAA+ ATPase. Assembly of SspB Dimers with ssrA-Tagged Proteins and the ClpX Hexamer." Chem Biol 9(11);1237-45. PMID: 12445774

Wah03: Wah DA, Levchenko I, Rieckhof GE, Bolon DN, Baker TA, Sauer RT (2003). "Flexible linkers leash the substrate binding domain of SspB to a peptide module that stabilizes delivery complexes with the AAA+ ClpXP protease." Mol Cell 12(2);355-63. PMID: 14536075

Wawrzynow95: Wawrzynow A, Wojtkowiak D, Marszalek J, Banecki B, Jonsen M, Graves B, Georgopoulos C, Zylicz M (1995). "The ClpX heat-shock protein of Escherichia coli, the ATP-dependent substrate specificity component of the ClpP-ClpX protease, is a novel molecular chaperone." EMBO J 14(9);1867-77. PMID: 7743994

Wegrzyn: Wegrzyn A, Czyz A, Gabig M, Wegrzyn G "ClpP/ClpX-mediated degradation of the bacteriophage lambda O protein and regulation of lambda phage and lambda plasmid replication." Arch Microbiol 174(1-2);89-96. PMID: 10985747

Weichart03: Weichart D, Querfurth N, Dreger M, Hengge-Aronis R (2003). "Global role for ClpP-containing proteases in stationary-phase adaptation of Escherichia coli." J Bacteriol 185(1);115-25. PMID: 12486047

Welty97: Welty DJ, Jones JM, Nakai H (1997). "Communication of ClpXP protease hypersensitivity to bacteriophage Mu repressor isoforms." J Mol Biol 272(1);31-41. PMID: 9299335

Wojtkowiak93: Wojtkowiak D, Georgopoulos C, Zylicz M (1993). "Isolation and characterization of ClpX, a new ATP-dependent specificity component of the Clp protease of Escherichia coli." J Biol Chem 268(30);22609-17. PMID: 8226769

Wojtyra03: Wojtyra UA, Thibault G, Tuite A, Houry WA (2003). "The N-terminal zinc binding domain of ClpX is a dimerization domain that modulates the chaperone function." J Biol Chem 278(49);48981-90. PMID: 12937164

Yoo93: Yoo S., Seol J., Ha D., Goldberg A., Chung C. (1993). Data submission to EMBL/GenBank/DDBJ databases on 1993-07.

Yoo94: Yoo SJ, Seol JH, Kang MS, Ha DB, Chung CH (1994). "clpX encoding an alternative ATP-binding subunit of protease Ti (Clp) can be expressed independently from clpP in Escherichia coli." Biochem Biophys Res Commun 1994;203(2);798-804. PMID: 8093059

Zhou01: Zhou Y, Gottesman S, Hoskins JR, Maurizi MR, Wickner S (2001). "The RssB response regulator directly targets sigma(S) for degradation by ClpXP." Genes Dev 15(5);627-37. PMID: 11238382

Zolkiewski06: Zolkiewski M (2006). "A camel passes through the eye of a needle: protein unfolding activity of Clp ATPases." Mol Microbiol 61(5);1094-100. PMID: 16879409

Zylicz98: Zylicz M, Liberek K, Wawrzynow A, Georgopoulos C (1998). "Formation of the preprimosome protects lambda O from RNA transcription-dependent proteolysis by ClpP/ClpX." Proc Natl Acad Sci U S A 95(26);15259-63. PMID: 9860956

Other References Related to Gene Regulation

Maurizi90: Maurizi MR, Clark WP, Katayama Y, Rudikoff S, Pumphrey J, Bowers B, Gottesman S (1990). "Sequence and structure of Clp P, the proteolytic component of the ATP-dependent Clp protease of Escherichia coli." J Biol Chem 265(21);12536-45. PMID: 2197275

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

Viveiros07: Viveiros M, Dupont M, Rodrigues L, Couto I, Davin-Regli A, Martins M, Pages JM, Amaral L (2007). "Antibiotic stress, genetic response and altered permeability of E. coli." PLoS ONE 2;e365. PMID: 17426813

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


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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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