{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:35:13Z","timestamp":1792701313781,"version":"4.5.0"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Bacteria as unicellular organisms are most directly exposed to changes in environmental growth conditions like temperature increase. Severe heat stress causes massive protein misfolding and aggregation resulting in loss of essential proteins. To ensure survival and rapid growth resume during recovery periods bacteria are equipped with cellular disaggregases, which solubilize and reactivate aggregated proteins. These disaggregases are members of the Hsp100\/AAA+ protein family, utilizing the energy derived from ATP hydrolysis to extract misfolded proteins from aggregates via a threading activity. Here, we describe the two best characterized bacterial Hsp100\/AAA+ disaggregases, ClpB and ClpG, and compare their mechanisms and regulatory modes. The widespread ClpB disaggregase requires cooperation with an Hsp70 partner chaperone, which targets ClpB to protein aggregates. Furthermore, Hsp70 activates ClpB by shifting positions of regulatory ClpB M-domains from a repressed to a derepressed state. ClpB activity remains tightly controlled during the disaggregation process and high ClpB activity states are likely restricted to initial substrate engagement. The recently identified ClpG (ClpK) disaggregase functions autonomously and its activity is primarily controlled by substrate interaction. ClpG provides enhanced heat resistance to selected bacteria including pathogens by acting as a more powerful disaggregase. This disaggregase expansion reflects an adaption of bacteria to extreme temperatures experienced during thermal based sterilization procedures applied in food industry and medicine. Genes encoding for ClpG are transmissible by horizontal transfer, allowing for rapid spreading of extreme bacterial heat resistance and posing a threat to modern food production.<\/jats:p>","DOI":"10.3389\/fmolb.2021.681439","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:28:05Z","timestamp":1620088085000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":34,"title":["Resisting the Heat: Bacterial Disaggregases Rescue Cells From Devastating Protein Aggregation"],"prefix":"10.3389","volume":"8","author":[{"given":"Panagiotis","family":"Katikaridis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Bohl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Mogk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2991","DOI":"10.1016\/j.febslet.2009.08.020","article-title":"DnaK-mediated association of ClpB to protein aggregates. A bichaperone network at the aggregate surface.","volume":"583","author":"Acebron","year":"2009","journal-title":"FEBS Lett."},{"key":"B2","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/s41586-020-1964-y","article-title":"Processive extrusion of polypeptide loops by a Hsp100 disaggregase.","volume":"578","author":"Avellaneda","year":"2020","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"34940","DOI":"10.1074\/jbc.m505653200","article-title":"The amino-terminal domain of ClpB supports binding to strongly aggregated proteins.","volume":"280","author":"Barnett","year":"2005","journal-title":"J. Biol. Chem."},{"key":"B4","doi-asserted-by":"publisher","first-page":"47160","DOI":"10.1074\/jbc.m207853200","article-title":"The N terminus of ClpB from Thermus thermophilus is not essential for the chaperone activity.","volume":"277","author":"Beinker","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1099\/jmm.0.032698-0","article-title":"The newly discovered ClpK protein strongly promotes survival of Klebsiella pneumoniae biofilm subjected to heat shock.","author":"Bojer","year":"2011","journal-title":"J. Med. Microbiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.resmic.2012.11.005","article-title":"ClpP-dependent and -independent activities encoded by the polycistronic clpK-encoding locus contribute to heat shock survival in Klebsiella pneumoniae.","volume":"164","author":"Bojer","year":"2013","journal-title":"Res. Microbiol."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015467","article-title":"Heat resistance mediated by a new plasmid encoded Clp ATPase, ClpK, as a possible novel mechanism for nosocomial persistence of Klebsiella pneumoniae.","volume":"5","author":"Bojer","year":"2010","journal-title":"PLoS One"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.00579","article-title":"Turn up the heat-food and clinical Escherichia coli isolates feature two transferrable loci of heat resistance.","volume":"8","author":"Boll","year":"2017","journal-title":"Front. Microbiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"3599","DOI":"10.1128\/jb.187.10.3599-3601.2005","article-title":"Localization of chaperones DnaK and GroEL in bacterial inclusion bodies.","volume":"187","author":"Carrio","year":"2005","journal-title":"J. Bacteriol."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.02481","article-title":"Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation.","volume":"3","author":"Carroni","year":"2014","journal-title":"Elife"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1128\/jb.186.4.1165-1174.2004","article-title":"clpB, a novel member of the Listeria monocytogenes CtsR regulon, is involved in virulence but not in general stress tolerance.","volume":"186","author":"Chastanet","year":"2004","journal-title":"J. Bacteriol."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1701726","article-title":"Structural pathway of regulated substrate transfer and threading through an Hsp100 disaggregase.","volume":"3","author":"Deville","year":"2017","journal-title":"Sci. Adv."},{"key":"B13","doi-asserted-by":"publisher","first-page":"3433","DOI":"10.1016\/j.celrep.2019.05.075","article-title":"Two-Step activation mechanism of the ClpB disaggregase for sequential substrate threading by the main ATPase motor.","volume":"27","author":"Deville","year":"2019","journal-title":"Cell Rep."},{"key":"B14","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1111\/j.1365-2672.2011.04943.x","article-title":"Characterization of an extremely heat-resistant Escherichia coli obtained from a beef processing facility.","volume":"110","author":"Dlusskaya","year":"2011","journal-title":"J. Appl. Microbiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"11138","DOI":"10.1073\/pnas.0703980104","article-title":"Collaboration between the ClpB AAA+ remodeling protein and the DnaK chaperone system.","volume":"104","author":"Doyle","year":"","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B16","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/nsmb1198","article-title":"Asymmetric deceleration of ClpB or Hsp104 ATPase activity unleashes protein-remodeling activity.","volume":"14","author":"Doyle","year":"","journal-title":"Nat. Struct. Mol. Biol."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24140-5","article-title":"Activation of the DnaK-ClpB complex is regulated by the properties of the bound substrate.","volume":"8","author":"Fernandez-Higuero","year":"2018","journal-title":"Sci. Rep."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1111\/j.1365-2958.2004.04368.x","article-title":"Clp ATPases are required for stress tolerance, intracellular replication and biofilm formation in Staphylococcus aureus.","volume":"54","author":"Frees","year":"2004","journal-title":"Mol. Microbiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1002\/pro.3743","article-title":"Stairway to translocation: AAA+ motor structures reveal the mechanisms of ATP-dependent substrate translocation.","volume":"29","author":"Gates","year":"2020","journal-title":"Protein Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1126\/science.aan1052","article-title":"Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104.","volume":"357","author":"Gates","year":"2017","journal-title":"Science"},{"key":"B21","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1128\/jb.186.1.179-191.2004","article-title":"Fine-tuning in regulation of Clp protein content in Bacillus subtilis.","volume":"186","author":"Gerth","year":"2004","journal-title":"J. Bacteriol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14164","article-title":"YocM a small heat shock protein can protect Bacillus subtilis cells during salt stress.","volume":"112","author":"Hantke","year":"2018","journal-title":"Mol. Microbiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.molcel.2006.11.008","article-title":"M domains couple the ClpB threading motor with the DnaK chaperone activity.","volume":"25","author":"Haslberger","year":"2007","journal-title":"Mol. Cell"},{"key":"B24","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/nsmb.1425","article-title":"Protein disaggregation by the AAA+ chaperone ClpB involves partial threading of looped polypeptide segments.","volume":"15","author":"Haslberger","year":"2008","journal-title":"Nat. Struct. Mol. Biol."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.21516","article-title":"Structural basis for the disaggregase activity and regulation of Hsp104.","volume":"5","author":"Heuck","year":"2016","journal-title":"Elife"},{"key":"B26","doi-asserted-by":"publisher","first-page":"22233","DOI":"10.1073\/pnas.0911937106","article-title":"Coupling ATP utilization to protein remodeling by ClpB, a hexameric AAA+ protein.","volume":"106","author":"Hoskins","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B27","doi-asserted-by":"publisher","first-page":"11037","DOI":"10.1073\/pnas.172378899","article-title":"ClpAP and ClpXP degrade proteins with tags located in the interior of the primary sequence.","volume":"99","author":"Hoskins","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2021.02.002","article-title":"Split conformation of Chaetomium thermophilum Hsp104 disaggregase.","author":"Inoue","year":"2021","journal-title":"Structure"},{"key":"B29","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.cell.2013.11.047","article-title":"Potentiated Hsp104 variants antagonize diverse proteotoxic misfolding events.","volume":"156","author":"Jackrel","year":"2014","journal-title":"Cell"},{"key":"B30","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1074\/jbc.273.1.459","article-title":"Versatile action of Escherichia coli ClpXP as protease or molecular chaperone for bacteriophage Mu transposition.","volume":"273","author":"Jones","year":"1998","journal-title":"J. Biol. Chem."},{"key":"B31","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1111\/mmi.14614","article-title":"A recently isolated human commensal Escherichia coli ST10 clone member mediates enhanced thermotolerance and tetrathionate respiration on a P1 phage-derived IncY plasmid.","volume":"115","author":"Kamal","year":"2021","journal-title":"Mol. Microbiol."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3390\/biom9120815","article-title":"ClpG provides increased heat resistance by acting as superior disaggregase.","volume":"9","author":"Katikaridis","year":"2019","journal-title":"Biomolecules"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100460","article-title":"Basic mechanism of the autonomous ClpG disaggregase.","volume":"24","author":"Katikaridis","year":"2021","journal-title":"J. Biol. Chem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"14242","DOI":"10.1021\/bi035573d","article-title":"Structure and function of the middle domain of ClpB from Escherichia coli.","volume":"42","author":"Kedzierska","year":"2003","journal-title":"Biochemistry"},{"key":"B35","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1111\/j.1365-2958.2008.06438.x","article-title":"Localization of general and regulatory proteolysis in Bacillus subtilis cells.","volume":"70","author":"Kirstein","year":"2008","journal-title":"Mol. Microbiol."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.15159","article-title":"Adenosine diphosphate restricts the protein remodeling activity of the Hsp104 chaperone to Hsp70 assisted disaggregation.","volume":"5","author":"Klosowska","year":"2016","journal-title":"Elife"},{"key":"B37","doi-asserted-by":"publisher","first-page":"2644","DOI":"10.1016\/j.celrep.2020.01.110","article-title":"The non-dominant AAA+ ring in the ClpAP protease functions as an anti-stalling motor to accelerate protein unfolding and translocation.","volume":"30","author":"Kotamarthi","year":"2020","journal-title":"Cell Rep."},{"key":"B38","doi-asserted-by":"publisher","first-page":"3360","DOI":"10.1128\/jb.176.11.3360-3367.1994","article-title":"Stress induction of clpC in Bacillus subtilis and its involvement in stress tolerance.","volume":"176","author":"Kruger","year":"1994","journal-title":"J. Bacteriol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3259","DOI":"10.1128\/jb.182.11.3259-3265.2000","article-title":"The clp proteases of Bacillus subtilis are directly involved in degradation of misfolded proteins.","volume":"182","author":"Kruger","year":"2000","journal-title":"J. Bacteriol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"4378","DOI":"10.1016\/j.jmb.2016.09.003","article-title":"Bacterial and Yeast AAA+ disaggregases ClpB and Hsp104 operate through conserved mechanism involving cooperation with Hsp70.","volume":"428","author":"Kummer","year":"2016","journal-title":"J. Mol. Biol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"E273","DOI":"10.1073\/pnas.1712051115","article-title":"Stand-alone ClpG disaggregase confers superior heat tolerance to bacteria.","volume":"115","author":"Lee","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B42","doi-asserted-by":"publisher","first-page":"4511","DOI":"10.1111\/1462-2920.12915","article-title":"A novel protein quality control mechanism contributes to heat shock resistance of worldwide-distributed Pseudomonas aeruginosa clone C strains.","volume":"17","author":"Lee","year":"2015","journal-title":"Environ. Microbiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"8513","DOI":"10.1073\/pnas.1217988110","article-title":"Heat shock protein (Hsp) 70 is an activator of the Hsp104 motor.","volume":"110","author":"Lee","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B44","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.celrep.2018.12.037","article-title":"Cryo-EM structures of the Hsp104 protein disaggregase captured in the ATP conformation.","volume":"26","author":"Lee","year":"2019","journal-title":"Cell Rep"},{"key":"B45","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0092-8674(03)00807-9","article-title":"The structure of ClpB. A molecular chaperone that rescues proteins from an aggregated state.","volume":"115","author":"Lee","year":"2003","journal-title":"Cell"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01763","article-title":"Some like it hot: heat resistance of Escherichia coli in food.","volume":"7","author":"Li","year":"2016","journal-title":"Front. Microbiol."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025777","article-title":"Transcriptome analysis of adaptive heat shock response of Streptococcus thermophilus.","volume":"6","author":"Li","year":"2011","journal-title":"PLoS One"},{"key":"B48","doi-asserted-by":"publisher","first-page":"2857","DOI":"10.1074\/jbc.M112.387589","article-title":"Disruption of ionic interactions between the nucleotide binding domain 1 (n.d.) and middle (M) domain in Hsp100 disaggregase unleashes toxic hyperactivity and partial independence from Hsp70.","volume":"288","author":"Lipinska","year":"2013","journal-title":"J. Biol. Chem."},{"key":"B49","doi-asserted-by":"publisher","first-page":"29139","DOI":"10.1074\/jbc.m403777200","article-title":"Evidence for an unfolding\/threading mechanism for protein disaggregation by Saccharomyces cerevisiae Hsp104.","volume":"279","author":"Lum","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.fm.2019.103400","article-title":"Characterization of Escherichia coli possessing the locus of heat resistance isolated from human cases of acute gastroenteritis.","volume":"88","author":"Ma","year":"2020","journal-title":"Food Microbiol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"8622","DOI":"10.3168\/jds.2016-11076","article-title":"Short communication: Heat-resistant Escherichia coli as potential persistent reservoir of extended-spectrum beta-lactamases and Shiga toxin-encoding phages in dairy.","volume":"99","author":"Marti","year":"2016","journal-title":"J. Dairy Sci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1016\/j.chembiol.2019.05.008","article-title":"Toxic activation of an AAA+ protease by the antibacterial drug Cyclomarin A.","volume":"26","author":"Maurer","year":"2019","journal-title":"Cell Chem. Biol."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2015.00058","article-title":"Insights into the molecular mechanism of allostery in Hsp70s.","volume":"2","author":"Mayer","year":"2015","journal-title":"Front. Mol. Biosci."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09474-6","article-title":"Tunable microsecond dynamics of an allosteric switch regulate the activity of a AAA+ disaggregation machine.","volume":"10","author":"Mazal","year":"2019","journal-title":"Nat. Commun."},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.00932","article-title":"Genetic determinants of heat resistance in Escherichia coli.","volume":"6","author":"Mercer","year":"2015","journal-title":"Front. Microbiol."},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01400-17","article-title":"Functional analysis of genes comprising the locus of heat resistance in Escherichia coli.","volume":"83","author":"Mercer","year":"2017","journal-title":"Appl. Environ. Microbiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"4610","DOI":"10.1128\/jb.00287-06","article-title":"Involvement of Bacillus subtilis ClpE in CtsR degradation and protein quality control.","volume":"188","author":"Miethke","year":"2006","journal-title":"J. Bacteriol."},{"key":"B58","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1074\/jbc.M209686200","article-title":"Roles of individual domains and conserved motifs of the AAA+ chaperone ClpB in oligomerization, ATP-hydrolysis and chaperone activity.","volume":"278","author":"Mogk","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B59","doi-asserted-by":"publisher","first-page":"6934","DOI":"10.1093\/emboj\/18.24.6934","article-title":"Identification of thermolabile E. coli proteins: prevention and reversion of aggregation by DnaK and ClpB.","volume":"18","author":"Mogk","year":"1999","journal-title":"EMBO J."},{"key":"B60","doi-asserted-by":"publisher","first-page":"5788","DOI":"10.1073\/pnas.91.13.5788","article-title":"MecB of Bacillus subtilis, a member of the ClpC ATPase family, is a pleiotropic regulator controlling competence gene expression and growth at high temperature.","volume":"91","author":"Msadek","year":"1994","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1038\/nsmb.2441","article-title":"A tightly regulated molecular toggle controls AAA+ disaggregase.","volume":"19","author":"Oguchi","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1146\/annurev-physiol-021317-121303","article-title":"Mechanical protein unfolding and degradation.","volume":"80","author":"Olivares","year":"2018","journal-title":"Annu. Rev. Physiol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"5279","DOI":"10.1016\/s0021-9258(18)42763-9","article-title":"DnaK, hsp73, and their molten globules. Two different ways heat shock proteins respond to heat.","volume":"267","author":"Palleros","year":"1992","journal-title":"J. Biol. Chem."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1111\/febs.13228","article-title":"ClpL is a chaperone without auxiliary factors.","volume":"282","author":"Park","year":"2015","journal-title":"FEBS J."},{"key":"B65","doi-asserted-by":"publisher","first-page":"3543","DOI":"10.3168\/jds.2012-6174","article-title":"Short communication: heat resistance of Escherichia coli strains in raw milk at different subpasteurization conditions.","volume":"96","author":"Peng","year":"2013","journal-title":"J. Dairy Sci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.molcel.2018.10.022","article-title":"ATP-dependent dynamic protein aggregation regulates bacterial dormancy depth critical for antibiotic tolerance.","volume":"73","author":"Pu","year":"2019","journal-title":"Mol. Cell"},{"key":"B67","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/s41580-019-0183-6","article-title":"The molecular principles governing the activity and functional diversity of AAA+ proteins.","volume":"21","author":"Puchades","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10150-y","article-title":"Structural basis for substrate gripping and translocation by the ClpB AAA+ disaggregase.","volume":"10","author":"Rizo","year":"2019","journal-title":"Nat. Commun."},{"key":"B69","doi-asserted-by":"publisher","first-page":"E6872","DOI":"10.1073\/pnas.1512783112","article-title":"ClpB N-terminal domain plays a regulatory role in protein disaggregation.","volume":"112","author":"Rosenzweig","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1126\/science.1233066","article-title":"Unraveling the mechanism of protein disaggregation through a ClpB-DnaK interaction.","volume":"339","author":"Rosenzweig","year":"2013","journal-title":"Science"},{"key":"B71","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1038\/s41580-019-0133-3","article-title":"The Hsp70 chaperone network.","volume":"20","author":"Rosenzweig","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.1091\/mbc.e02-08-0502","article-title":"Dominant gain-of-function mutations in Hsp104p reveal crucial roles for the middle region.","volume":"15","author":"Schirmer","year":"2004","journal-title":"Mol. Biol. Cell"},{"key":"B73","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1006\/jmbi.2001.4455","article-title":"The chaperone function of ClpB from Thermus thermophilus depends on allosteric interactions of its two ATP-binding sites.","volume":"306","author":"Schlee","year":"2001","journal-title":"J. Mol. Biol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/nsmb787","article-title":"Substrate recognition by the AAA+ chaperone ClpB.","volume":"11","author":"Schlieker","year":"2004","journal-title":"Nat. Struct. Mol. Biol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"2306","DOI":"10.1073\/pnas.0535717100","article-title":"MecA, an adaptor protein necessary for ClpC chaperone activity.","volume":"100","author":"Schlothauer","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B76","doi-asserted-by":"publisher","first-page":"5889","DOI":"10.1002\/anie.201101740","article-title":"The natural product cyclomarin kills Mycobacterium tuberculosis by targeting the ClpC1 subunit of the caseinolytic protease.","volume":"50","author":"Schmitt","year":"2011","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1038\/nsmb.2442","article-title":"Hsp70 proteins bind Hsp100 regulatory M domains to activate AAA+ disaggregase at aggregate surfaces.","volume":"19","author":"Seyffer","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"4254","DOI":"10.1128\/jb.173.14.4254-4262.1991","article-title":"ClpB is the Escherichia coli heat shock protein F84.1.","volume":"173","author":"Squires","year":"1991","journal-title":"J. Bacteriol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1002\/2211-5463.12509","article-title":"The amino-terminal domain of Mycobacterium tuberculosis ClpB protein plays a crucial role in its substrate disaggregation activity.","volume":"8","author":"Tripathi","year":"2018","journal-title":"FEBS Open Bio."},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2020.151402","article-title":"ClpB is an essential stress regulator of Mycobacterium tuberculosis and endows survival advantage to dormant bacilli.","volume":"310","author":"Tripathi","year":"2020","journal-title":"Int. J. Med. Microbiol."},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04587-w","article-title":"Dynamic structural states of ClpB involved in its disaggregation function.","volume":"9","author":"Uchihashi","year":"2018","journal-title":"Nat. Commun."},{"key":"B82","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1016\/j.cell.2015.08.041","article-title":"Reversible, specific, active aggregates of endogenous proteins assemble upon heat stress.","volume":"162","author":"Wallace","year":"2015","journal-title":"Cell"},{"key":"B83","doi-asserted-by":"publisher","first-page":"5804","DOI":"10.1074\/jbc.m109349200","article-title":"Roles of the two ATP binding sites of ClpB from Thermus thermophilus.","volume":"277","author":"Watanabe","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B84","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/43481","article-title":"Global unfolding of a substrate protein by the Hsp100 chaperone ClpA.","volume":"401","author":"Weber-Ban","year":"1999","journal-title":"Nature"},{"key":"B85","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/j.cell.2004.11.027","article-title":"Thermotolerance requires refolding of aggregated proteins by substrate translocation through the central pore of ClpB.","volume":"119","author":"Weibezahn","year":"2004","journal-title":"Cell"},{"key":"B86","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1038\/emboj.2009.412","article-title":"Quantitative and spatio-temporal features of protein aggregation in Escherichia coli and consequences on protein quality control and cellular ageing.","volume":"29","author":"Winkler","year":"2010","journal-title":"EMBO J."},{"key":"B87","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1083\/jcb.201201074","article-title":"Hsp70 targets Hsp100 chaperones to substrates for protein disaggregation and prion fragmentation.","volume":"198","author":"Winkler","year":"2012","journal-title":"J. Cell Biol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"9384","DOI":"10.1073\/pnas.1921968117","article-title":"Structural and kinetic basis for the regulation and potentiation of Hsp104 function.","volume":"117","author":"Ye","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B89","doi-asserted-by":"publisher","first-page":"E9560","DOI":"10.1073\/pnas.1810648115","article-title":"ATP hydrolysis-coupled peptide translocation mechanism of Mycobacterium tuberculosis ClpB.","volume":"115","author":"Yu","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2021.681439\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:28:11Z","timestamp":1620088091000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2021.681439\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,4]]},"references-count":89,"alternative-id":["10.3389\/fmolb.2021.681439"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2021.681439","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,4]]},"article-number":"681439"}}