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PreprintCited by 14Heat shock proteins researchBacterial Genetics and BiotechnologyProtein purification and stability

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The Listeria monocytogenes persistence factor ClpL is a potent stand-alone disaggregase

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Bohl, Valentin, Hollmann, Nele Merret, Melzer, Tobias, Katikaridis, Panagiotis, Meins, Lena, Simon, Bernd, Flemming, Dirk, Sinning, Irmgard, Hennig, Janosch, Mogk, Axel·2024·eLife
DOI 10.7554/elife.92746.2PMC PMC11006417

Preprint — published as 10.7554/elife.92746.3 · Paper page

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Abstract

Abstract Heat stress can cause cell death by triggering the aggregation of essential proteins. In bacteria, aggregated proteins are rescued by the canonical Hsp70/AAA+ (ClpB) bi-chaperone disaggregase. Man-made, severe stress conditions applied during e.g. food-processing represent a novel threat for bacteria by exceeding the capacity of the Hsp70/ClpB system. Here, we report on the potent autonomous AAA+ disaggregase ClpL from Listeria monocytogenes that provides enhanced heat resistance to the food-borne pathogen enabling persistence in adverse environments. ClpL shows increased thermal stability and enhanced disaggregation power compared to Hsp70/ClpB, enabling it to withstand severe heat stress and to solubilize tight aggregates. ClpL binds to protein aggregates via aromatic residues present in its N-terminal domain (NTD) that adopts a partially folded and dynamic conformation. Target specificity is achieved by simultaneous interactions of multiple NTDs with the aggregate surface. ClpL shows remarkable structural plasticity by forming diverse higher assembly states through interacting ClpL rings. NTDs become largely sequestered upon ClpL ring interactions. Stabilizing ring assemblies by engineered disulfide bonds strongly reduces disaggregation activity, suggesting that they represent storage states.

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Research works printed but not linked: 65

  1. 2013, PINT: a software for integration of peak volumes and extraction of relaxation rates, J Biomol NMR, 56, 191, 10.1007/s10858-013-9737-7 · DOI
  2. 2006, Trend of amino acid composition of proteins of different taxa, J Bioinform Comput Biol, 4, 597, 10.1142/S0219720006002016 · DOI
  3. 2010, Heat resistance mediated by a new plasmid encoded Clp ATPase, ClpK, as a possible novel mechanism for nosocomial persistence of Klebsiella pneumoniae, PLoS One, 5, e15467, 10.1371/journal.pone.0015467 · DOI
  4. 2017, Turn Up the Heat-Food and Clinical Escherichia coli Isolates Feature Two Transferrable Loci of Heat Resistance, Front Microbiol, 8, 579
  5. 2018, Resistance of Listeria monocytogenes to Stress Conditions Encountered in Food and Food Processing Environments, Front Microbiol, 9, 2700, 10.3389/fmicb.2018.02700 · DOI
  6. 2022, Unique structural features govern the activity of a human mitochondrial AAA+ disaggregase, Skd3, Cell Rep, 40, 111408, 10.1016/j.celrep.2022.111408 · DOI · Paper page
  7. 1995, NMRPipe: a multidimensional spectral processing system based on UNIX pipes, J Biomol NMR, 6, 277
  8. 2017, Structural pathway of regulated substrate transfer and threading through an Hsp100 disaggregase, Sci Adv, 3, e1701726, 10.1126/sciadv.1701726 · DOI
  9. 2022, Cryo-EM structures of human p97 double hexamer capture potentiated ATPase-competent state, Cell Discov, 8, 19, 10.1038/s41421-022-00379-1 · DOI
  10. 2015, Coordinated Ribosomal ITS2 RNA Processing by the Las1 Complex Integrating Endonuclease, Polynucleotide Kinase, and Exonuclease Activities, Mol Cell, 60, 808, 10.1016/j.molcel.2015.10.021 · DOI
  11. 2023, Dodecamer assembly of a metazoan AAA(+) chaperone couples substrate extraction to refolding, Sci Adv, 9, eadf5336, 10.1126/sciadv.adf5336 · DOI
  12. 2008, Protein disaggregation by the AAA+ chaperone ClpB involves partial threading of looped polypeptide segments, Nat Struct Mol Biol, 15, 641, 10.1038/nsmb.1425 · DOI
  13. 1993, Two genes present on a transposon-like structure in Lactococcus lactis are involved in a Clp-family proteolytic activity, Mol Microbiol, 7, 957, 10.1111/j.1365-2958.1993.tb01187.x · DOI
  14. 2021, Entropic Inhibition: How the Activity of a AAA+ Machine Is Modulated by Its Substrate-Binding Domain, ACS chemical biology, 16, 775, 10.1021/acschembio.1c00156 · DOI
  15. 2016, Efflux pump-mediated benzalkonium chloride resistance in Listeria monocytogenes isolated from retail food, Int J Food Microbiol, 217, 141, 10.1016/j.ijfoodmicro.2015.10.022 · DOI
  16. 2021a, A recently isolated human commensal Escherichia coli ST10 clone member mediates enhanced thermotolerance and tetrathionate respiration on a P1 phage-derived IncY plasmid, Mol Microbiol, 115, 255, 10.1111/mmi.14614 · DOI
  17. 2021b, Horizontal Transmission of Stress Resistance Genes Shape the Ecology of Beta- and Gamma-Proteobacteria, Front Microbiol, 12, 696522, 10.3389/fmicb.2021.696522 · DOI
  18. 2019, ClpG Provides Increased Heat Resistance by Acting as Superior Disaggregase, Biomolecules, 9
  19. 2023, Structural basis of aggregate binding by the AAA+ disaggregase ClpG, bioRxiv
  20. 2020, ClpL is a functionally active tetradecameric AAA+ chaperone, distinct from hexameric/dodecameric ones, FASEB J, 34, 14353, 10.1096/fj.202000843R · DOI
  21. 2009, Adapting the machine: adaptor proteins for Hsp100/Clp and AAA+ proteases, Nature reviews Microbiology, 7, 589, 10.1038/nrmicro2185 · DOI
  22. 2010, Independent evolution of the core domain and its flanking sequences in small heat shock proteins, FASEB J, 24, 3633, 10.1096/fj.10-156992 · DOI
  23. 2003, Effect of heat shock and mutations in ClpL and ClpP on virulence gene expression in Streptococcus pneumoniae, Infect Immun, 71, 3757, 10.1128/IAI.71.7.3757-3765.2003 · DOI
  24. 1994, Plasmid-borne cadmium resistance genes in Listeria monocytogenes are similar to cadA and cadC of Staphylococcus aureus and are induced by cadmium, J Bacteriol, 176, 3040, 10.1128/jb.176.10.3040-3048.1994 · DOI
  25. 2018, Stand-alone ClpG disaggregase confers superior heat tolerance to bacteria, Proc Natl Acad Sci U S A, 115, E273
  26. 2023, Structural basis of impaired disaggregase function in the oxidation-sensitive SKD3 mutant causing 3-methylglutaconic aciduria, Nature communications, 14, 2028, 10.1038/s41467-023-37657-9 · DOI
  27. 2015, NMRFAM-SPARKY: enhanced software for biomolecular NMR spectroscopy, Bioinformatics, 31, 1325, 10.1093/bioinformatics/btu830 · DOI
  28. 2011, Transcriptome analysis of adaptive heat shock response of Streptococcus thermophilus, PLoS One, 6, e25777, 10.1371/journal.pone.0025777 · DOI
  29. 2013, Disruption of ionic interactions between the nucleotide binding domain 1 (NBD1) and middle (M) domain in Hsp100 disaggregase unleashes toxic hyperactivity and partial independence from Hsp70, J Biol Chem, 288, 2857, 10.1074/jbc.M112.387589 · DOI
  30. 2011, Single particle electron microscopy reconstruction of the exosome complex using the random conical tilt method, J Vis Exp
  31. 2008, Acid and heat tolerance of persistent and nonpersistent Listeria monocytogenes food plant strains, Lett Appl Microbiol, 46, 276
  32. 2019, Toxic Activation of an AAA+ Protease by the Antibacterial Drug Cyclomarin A, Cell Chem Biol, 26, 1169, 10.1016/j.chembiol.2019.05.008 · DOI
  33. 2022, ColabFold: making protein folding accessible to all, Nat Methods, 19, 679, 10.1038/s41592-022-01488-1 · DOI · Paper page
  34. 2003, Roles of individual domains and conserved motifs of the AAA+ chaperone ClpB in oligomerization, ATP-hydrolysis and chaperone activity, J Biol Chem, 278, 15
  35. 1999, Identification of thermolabile E. coli proteins: prevention and reversion of aggregation by DnaK and ClpB, EMBO J, 18, 6934, 10.1093/emboj/18.24.6934 · DOI
  36. 2022, BacPROTACs mediate targeted protein degradation in bacteria, Cell, 185, 2338, 10.1016/j.cell.2022.05.009 · DOI · Paper page
  37. 2019, Plasmids contribute to food processing environment-associated stress survival in three Listeria monocytogenes ST121, ST8, and ST5 strains, Int J Food Microbiol, 299, 39, 10.1016/j.ijfoodmicro.2019.03.016 · DOI
  38. 2017, Comprehensive analysis of NMR data using advanced line shape fitting, J Biomol NMR, 69, 93, 10.1007/s10858-017-0141-6 · DOI
  39. 2012, A tightly regulated molecular toggle controls AAA+ disaggregase, Nat Struct Mol Biol, 19, 1338, 10.1038/nsmb.2441 · DOI
  40. 1992, DnaK, hsp73, and their molten globules. Two different ways heat shock proteins respond to heat, J Biol Chem, 267, 5279, 10.1016/S0021-9258(18)42763-9 · DOI
  41. 2015, ClpL is a chaperone without auxiliary factors, FEBS J, 282, 1352, 10.1111/febs.13228 · DOI
  42. 2021, Virulence and Antibiotic Resistance Genes in Listeria monocytogenes Strains Isolated From Ready-to-Eat Foods in Chile, Front Microbiol, 12, 796040
  43. 2017, Heat Resistance Mediated by pLM58 Plasmid-Borne ClpL in Listeria monocytogenes, mSphere, 2
  44. 1990, Transferable plasmid-mediated antibiotic resistance in Listeria monocytogenes, Lancet, 335, 1422, 10.1016/0140-6736(90)91447-I · DOI
  45. 2020, The molecular principles governing the activity and functional diversity of AAA+ proteins, Nat Rev Mol Cell Biol, 21, 43, 10.1038/s41580-019-0183-6 · DOI
  46. 2023, Whole-genome sequencing of Listeria innocua recovered from retail milk and dairy products in Egypt, Front Microbiol, 14, 1160244, 10.3389/fmicb.2023.1160244 · DOI
  47. 2015, ClpB N-terminal domain plays a regulatory role in protein disaggregation, Proc Natl Acad Sci U S A, 112, E6872
  48. 1999, Heteronuclear multidimensional NMR experiments for the structure determination of proteins in solution employing pulsed field gradients, Progress in Nuclear Magnetic Resonance Spectroscopy, 34, 93, 10.1016/S0079-6565(98)00025-9 · DOI
  49. 2012, Hsp70 proteins bind Hsp100 regulatory M domains to activate AAA+ disaggregase at aggregate surfaces, Nat Struct Mol Biol, 19, 1347, 10.1038/nsmb.2442 · DOI
  50. 2022, The cytoprotective sequestration activity of small heat shock proteins is evolutionarily conserved, J Cell Biol, 221
  51. 2019, Improving the sensitivity of FT-NMR spectroscopy by apodization weighted sampling, J Biomol NMR, 73, 155, 10.1007/s10858-019-00243-7 · DOI
  52. 2022, Human mitochondrial AAA+ ATPase SKD3/CLPB assembles into nucleotide-stabilized dodecamers, Biochem Biophys Res Commun, 602, 21, 10.1016/j.bbrc.2022.02.101 · DOI
  53. 2008, ClpL is essential for induction of thermotolerance and is potentially part of the HrcA regulon in Lactobacillus gasseri, Proteomics, 8, 1029, 10.1002/pmic.200700925 · DOI
  54. 2005, Characterization of a mobile clpL gene from Lactobacillus rhamnosus, Appl Environ Microbiol, 71, 2061, 10.1128/AEM.71.4.2061-2069.2005 · DOI · Paper page
  55. 1998, Biochemical basis of SOS-induced mutagenesis in Escherichia coli: reconstitution of in vitro lesion bypass dependent on the UmuD’2C mutagenic complex and RecA protein, Proc Natl Acad Sci U S A, 95, 9755, 10.1073/pnas.95.17.9755 · DOI
  56. 2013, ClpL is required for folding of CtsR in Streptococcus mutans, J Bacteriol, 195, 576, 10.1128/JB.01743-12 · DOI
  57. 2022, Antibacterial peptide CyclomarinA creates toxicity by deregulating the Mycobacterium tuberculosis ClpC1-ClpP1P2 protease, J Biol Chem, 298, 102202, 10.1016/j.jbc.2022.102202 · DOI
  58. 1996, A new generation of the IMAGIC image processing system, J Struct Biol, 116, 17, 10.1006/jsbi.1996.0004 · DOI
  59. 2013, Distinct quaternary structures of the AAA+ Lon protease control substrate degradation, Proc Natl Acad Sci U S A, 110, E2002
  60. 2004, Thermotolerance Requires Refolding of Aggregated Proteins by Substrate Translocation through the Central Pore of ClpB, Cell, 119, 653, 10.1016/j.cell.2004.11.027 · DOI
  61. 2008, Coupling and dynamics of subunits in the hexameric AAA+ chaperone ClpB, J Mol Biol, 378, 178, 10.1016/j.jmb.2008.02.026 · DOI
  62. 2012, Hsp70 targets Hsp100 chaperones to substrates for protein disaggregation and prion fragmentation, J Cell Biol, 198, 387, 10.1083/jcb.201201074 · DOI
  63. 1994, The 13C chemical-shift index: a simple method for the identification of protein secondary structure using 13C chemical-shift data, J Biomol NMR, 4, 171
  64. 2023, Comprehensive structural characterization of the human AAA+ disaggregase CLPB in the apo- and substrate-bound states reveals a unique mode of action driven by oligomerization, PLoS Biol, 21, e3001987, 10.1371/journal.pbio.3001987 · DOI
  65. 1999, ClpB cooperates with DnaK, DnaJ, and GrpE in suppressing protein aggregation. A novel multi-chaperone system from Escherichia coli, J Biol Chem, 274, 28083, 10.1074/jbc.274.40.28083 · DOI

Metadata

Authors
Bohl, V., Hollmann, N. M., Melzer, T., Katikaridis, P., Meins, L., Simon, B., Flemming, D., Sinning, I., Hennig, J., & Mogk, A.
Affiliations
University of Geneva (CH)
Corresponding author
Mogk, Axel
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2024-03-20
Volume
12
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.92746.2
PMC
PMC11006417
OpenAlex
W4388762888
Cited by
14
References
1
Citations by year
2026: 5 · 2025: 6 · 2024: 3
FWCI
1.24
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • eLife (acceptedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Deutsche Forschungsgemeinschaft (MO970/7-1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
Keywords
Listeria monocytogenes, protein aggregation, heat stress, protein disaggregation, N-terminal domain, aromatic residues, disulfide bonds, thermal stability
MeSH terms
Animals, Estrus, Food, Humans, Listeria monocytogenes, Neural Tube Defects, Cell Death, HSP70 Heat-Shock Proteins

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