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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

Regulation summary diagram for clpX

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

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

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; the ssrA-tag interacts with pore loop regions (RKH loop; pore 1 loop and pore 2 loop) located in the central core of the ClpX hexamer [Siddiqui04, Farrell07, Martin07, Martin08, Martin08a]. The RKH loop, located at the entry to the central pore plays a role in determining substrate specificity [Farrell07]. Pore loop 1 (also called the axial pore loop) contains a conserved aromatic-hydrocarbon (Y153-V154) dipeptide; ClpX variants containing a Y153A substitution are defective in gripping ssrA tagged substrates to drive translocation and unfolding [Martin08a]. Axial pore loops function in a synergistic manner; in vitro the number of wild-type loops required for efficient degradation is dependent on the resistance of the protein substrate to mechanical unfolding [Iosefson15].

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 [Kim01c, 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 ClpX 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, Stinson15]

Gene Citations: [Li00, Rhodius05]

Locations: cytosol

Map Position: [456,650 -> 457,924] (9.84 centisomes, 35°)
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:IPR003959, InterPro:IN-FAMILY:IPR004487, InterPro:IN-FAMILY:IPR010603, 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

Gene-Reaction Schematic

Genetic Regulation Schematic

Genetic regulation schematic for clpX

GO Terms:
Biological Process:
Inferred from experimentGO:0006508 - proteolysis [Gottesman98, Wojtkowiak93]
Inferred from experimentGO:0043335 - protein unfolding [Maillard11]
Inferred from experimentGO:0051301 - cell division [Camberg11]
Inferred by computational analysisGO:0006457 - protein folding [GOA06, GOA01a]
Inferred by computational analysisGO:0016032 - viral process [UniProtGOA11a]
Molecular Function:
Inferred from experimentGO:0004176 - ATP-dependent peptidase activity [Gottesman98, Wojtkowiak93]
Inferred from experimentInferred by computational analysisGO:0005524 - ATP binding [UniProtGOA11a, GOA06, GOA01a, Grimaud98]
Inferred from experimentGO:0016887 - ATPase activity [Banecki01]
Inferred from experimentGO:0042802 - identical protein binding [Rajagopala14, Stinson13, Glynn09]
Inferred by computational analysisGO:0000166 - nucleotide binding [UniProtGOA11a]
Inferred by computational analysisGO:0008270 - zinc ion binding [GOA01a]
Inferred by computational analysisGO:0046872 - metal ion binding [UniProtGOA11a]
Inferred by computational analysisGO:0046983 - protein dimerization activity [GOA01a]
Inferred by computational analysisGO:0051082 - unfolded protein binding [GOA06, GOA01a]
Cellular Component:
Inferred from experimentInferred by computational analysisGO:0005829 - cytosol [DiazMejia09, Ishihama08, LopezCampistrou05]

MultiFun Terms: information transferprotein relatedchaperoning, repair (refolding)
information transferprotein relatedturnover, degradation
metabolismdegradation of macromoleculesproteins/peptides/glycopeptides

Essentiality data for clpX 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]

Curated 13-Jan-2006 by Shearer A, SRI International
Last-Curated 17-Feb-2015 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 (extended summary available)
         ClpX ATP-dependent protease specificity component and chaperone = (ClpX)6 (extended summary available)

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, Grimaud98].

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

Inferred from experiment

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

EC Number:

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.

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)

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 [Jones98a, 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, Zhou01b, 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 [Kim00a]. 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]. When visualised at the single molecule level, the unfolding and translocation of substrate by ClpXP occurs in physical steps of varying size (1-4nm) which lack defined order [Cordova14]

ClpXP is required for limitation of lambda phage early DNA replication during slow growth [Wegrzyn00].

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, Russell14]|

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

Enzymatic reaction of: protease (ClpXP)

Inferred from experiment

EC Number:

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 ClpX with features indicated

Feature Class Location Common Name Attached Group Citations Comment
Cleavage-of-Initial-Methionine 1    
Inferred from experiment[Wojtkowiak93]
UniProt: Removed.
Chain 2 -> 424    
Author statement[UniProt15]
UniProt: ATP-dependent Clp protease ATP-binding subunit ClpX.
Metal-Binding-Site 15    
Inferred from experiment[Donaldson03]
UniProt: Zinc.
Zn-Finger-Region 15 -> 40    
Inferred by computational analysis[UniProt15]
UniProt: C4-type.
Metal-Binding-Site 18    
Inferred from experiment[Donaldson03]
UniProt: Zinc.
Metal-Binding-Site 37    
Inferred from experiment[Donaldson03]
UniProt: Zinc.
Metal-Binding-Site 40    
Inferred from experiment[Donaldson03]
UniProt: Zinc.
Protein-Segment 65 -> 314 large AAA+ domain  
Author statement[Glynn12]
Nucleotide-Phosphate-Binding-Region 120 -> 127   ATP
Inferred from experiment[Stinson13, Glynn09]
UniProt: ATP.
Protein-Structure-Region 151 -> 155 pore loop 1 / axial pore loop  
Author statementInferred from experiment[Martin08a, Martin08a, Siddiqui04]
protrudes from every subunit into the central pore of the ClpX hexamer; functions in gripping substrates to drive translocation and unfolding
Mutagenesis-Variant 153    
Inferred from experiment[Martin08a, Siddiqui04]
alternate sequence Y → A; does not support degradation of substrates; defective in gripping substrates to drive translocation and unfolding
Mutagenesis-Variant 154    
Inferred from experiment[Siddiqui04]
alternate sequence V → F; defective in binding C1 tagged substrates
Mutagenesis-Variant 185    
Inferred from experiment[Stinson13]
UniProt: No ATP hydrolyis.
Protein-Structure-Region 191 -> 201 pore loop 2  
Inferred from experiment[Martin07]
role in recognising ssrA tagged substrates
Protein-Structure-Region 228 -> 230 RKH loop  
Author statementInferred from experiment[Farrell07, Farrell07]
critical for binding ssrA tagged substrates; plays a role in determining substrate specificity
Sequence-Conflict 268 -> 274    
Inferred by curator[Yoo94, UniProt15]
UniProt: (in Ref. 2; CAA80816).
Protein-Segment 315 -> 318 hinge region  
Author statement[Glynn12]
Protein-Segment 319 -> 424 small AAA+ domain  
Author statement[Glynn12]
Mutagenesis-Variant 370    
Inferred from experiment[Stinson13]
UniProt: No ATP hydrolyis.

Sequence Pfam Features

Protein sequence of ClpX with features indicated

Feature Class Location Citations Comment
Pfam PF06689 13 -> 50
Inferred by computational analysis[Finn14]
zf-C4_ClpX : ClpX C4-type zinc finger
Pfam PF07724 112 -> 310
Inferred by computational analysis[Finn14]
AAA_2 : AAA domain (Cdc48 subfamily)
Pfam PF10431 317 -> 395
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 Units

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram


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


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

Cordova14: Cordova JC, Olivares AO, Shin Y, Stinson BM, Calmat S, Schmitz KR, Aubin-Tam ME, Baker TA, Lang MJ, Sauer RT (2014). "Stochastic but highly coordinated protein unfolding and translocation by the ClpXP proteolytic machine." Cell 158(3);647-58. PMID: 25083874

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

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

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

Iosefson15: Iosefson O, Nager AR, Baker TA, Sauer RT (2015). "Coordinated gripping of substrate by subunits of a AAA+ proteolytic machine." Nat Chem Biol 11(3);201-206. PMID: 25599533

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

Jones98a: 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

Kim00a: 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

Kim01c: 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

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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

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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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