The Deinococcus protease PprI senses DNA damage by directly interacting with single-stranded DNA.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 Feb 2024
29 Feb 2024
Historique:
received:
19
05
2023
accepted:
16
02
2024
medline:
1
3
2024
pubmed:
1
3
2024
entrez:
29
2
2024
Statut:
epublish
Résumé
Bacteria have evolved various response systems to adapt to environmental stress. A protease-based derepression mechanism in response to DNA damage was characterized in Deinococcus, which is controlled by the specific cleavage of repressor DdrO by metallopeptidase PprI (also called IrrE). Despite the efforts to document the biochemical, physiological, and downstream regulation of PprI-DdrO, the upstream regulatory signal activating this system remains unclear. Here, we show that single-stranded DNA physically interacts with PprI protease, which enhances the PprI-DdrO interactions as well as the DdrO cleavage in a length-dependent manner both in vivo and in vitro. Structures of PprI, in its apo and complexed forms with single-stranded DNA, reveal two DNA-binding interfaces shaping the cleavage site. Moreover, we show that the dynamic monomer-dimer equilibrium of PprI is also important for its cleavage activity. Our data provide evidence that single-stranded DNA could serve as the signal for DNA damage sensing in the metalloprotease/repressor system in bacteria. These results also shed light on the survival and acquired drug resistance of certain bacteria under antimicrobial stress through a SOS-independent pathway.
Identifiants
pubmed: 38424107
doi: 10.1038/s41467-024-46208-9
pii: 10.1038/s41467-024-46208-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1892Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32370028
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32200016
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32222001
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : U1967217
Organisme : Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)
ID : LQ23C010002
Organisme : Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)
ID : LDQ23C050002
Informations de copyright
© 2024. The Author(s).
Références
Tubbs, A. & Nussenzweig, A. Endogenous DNA damage as a source of genomic instability in cancer. Cell 168, 644–656 (2017).
pubmed: 28187286
pmcid: 6591730
Huen, M. S. & Chen, J. The DNA damage response pathways: at the crossroad of protein modifications. Cell Res. 18, 8–16 (2008).
pubmed: 18087291
Marechal, A. & Zou, L. DNA Damage Sensing by the ATM and ATR Kinases. CSH Perspect. Biol. 5, a012716 (2013).
Jeggo, P. A. & Lobrich, M. Contribution of DNA repair and cell cycle checkpoint arrest to the maintenance of genomic stability. DNA Repair 5, 1192–1198 (2006).
pubmed: 16797253
Cox, M. M. & Battista, J. R. Deinococcus radiodurans - the consummate survivor. Nat. Rev. Microbiol. 3, 882–892 (2005).
pubmed: 16261171
Blasius, M., Sommer, S. & Hubscher, U. Deinococcus radiodurans: what belongs to the survival kit? Crit. Rev. Biochem. Mol. Biol. 43, 221–238 (2008).
pubmed: 18568848
Slade, D. & Radman, M. Oxidative stress resistance in Deinococcus radiodurans. Microbiol. Mol. Biol. Rev. 75, 133–191 (2011).
pubmed: 21372322
pmcid: 3063356
Lim, S., Jung, J. H., Blanchard, L. & de Groot, A. Conservation and diversity of radiation and oxidative stress resistance mechanisms in Deinococcus species. FEMS Microbiol. Rev. 43, 19–52 (2019).
pubmed: 30339218
Qi, H. Z. et al. Antioxidative system of Deinococcus radiodurans. Res. Microbiol. 171, 45–54 (2020).
pubmed: 31756434
Liu, Y. et al. Transcriptome dynamics of Deinococcus radiodurans recovering from ionizing radiation. Proc. Natl Acad. Sci. USA 100, 4191–4196 (2003).
pubmed: 12651953
pmcid: 153069
Battista, J. R. & Cox, M. M. Genome reconstitution in the extremely radiation resistant bacterium Deinococcus radiodurans. NATO Secur. Sci. 9, 341 (2006).
Selvam, K., Duncan, J. R., Tanaka, M. & Battista, J. R. DdrA, DdrD, and PprA: components of UV and mitomycin C resistance in Deinococcus radiodurans R1. PloS One 8, e69007 (2013).
pubmed: 23840905
pmcid: 3698191
Lockhart, J. S. & DeVeaux, L. C. The essential role of the Deinococcus radiodurans ssb gene in cell survival and radiation tolerance. PloS One 8, e71651 (2013).
pubmed: 23951213
pmcid: 3739723
Norais, C. A., Chitteni-Pattu, S., Wood, E. A., Inman, R. B. & Cox, M. M. DdrB protein, an alternative Deinococcus radiodurans SSB induced by ionizing radiation. J. Biol. Chem. 284, 21402–21411 (2009).
pubmed: 19515845
pmcid: 2755865
Kota, S., Charaka, V. K., Ringgaard, S., Waldor, M. K. & Misra, H. S. PprA contributes to Deinococcus radiodurans resistance to nalidixic acid, genome maintenance after DNA damage and interacts with deinococcal topoisomerases. PloS One 9, e85288 (2014).
pubmed: 24454836
pmcid: 3893189
Little, J. W. Mechanism of specific Lexa Cleavage - Autodigestion and the role of Reca Coprotease. Biochimie 73, 411–422 (1991).
pubmed: 1911941
Narumi, I. et al. The LexA protein from Deinococcus radiodurans is not involved in RecA induction following gamma irradiation. J. Bacteriol. 183, 6951–6956 (2001).
pubmed: 11698386
pmcid: 95538
Sheng, D., Zheng, Z., Tian, B., Shen, B. & Hua, Y. LexA analog (dra0074) is a regulatory protein that is irrelevant to recA induction. J. Biochem. 136, 787–793 (2004).
pubmed: 15671489
Jolivet, E. et al. Limited concentration of RecA delays DNA double-strand break repair in Deinococcus radiodurans R1. Mol. Microbiol. 59, 338–349 (2006).
pubmed: 16359339
Hua, Y. et al. PprI: a general switch responsible for extreme radioresistance of Deinococcus radiodurans. Biochem. Biophys. Res. Commun. 306, 354–360 (2003).
pubmed: 12804570
Lu, H. et al. Deinococcus radiodurans PprI switches on DNA damage response and cellular survival networks after radiation damage. Mol. Cell. Proteom. 8, 481–494 (2009).
Lu, H., Chen, H., Xu, G., Shah, A. M. & Hua, Y. DNA binding is essential for PprI function in response to radiation damage in Deinococcus radiodurans. DNA Repair. 11, 139–145 (2012).
pubmed: 22051194
Ludanyi, M. et al. Radiation response in Deinococcus deserti: IrrE is a metalloprotease that cleaves repressor protein DdrO. Mol. Microbiol. 94, 434–449 (2014).
pubmed: 25170972
Wang, Y. et al. Protease activity of PprI facilitates DNA damage response: Mn2+-dependence and substrate sequence-specificity of the proteolytic reaction. PloS One 10, e0122071 (2015).
pubmed: 25811789
pmcid: 4374696
Lu, H. et al. Structure and DNA damage-dependent derepression mechanism for the XRE family member DG-DdrO. Nucleic Acids Res. 47, 9925–9933 (2019).
pubmed: 31410466
pmcid: 6765133
de Groot, A. et al. Crystal structure of the transcriptional repressor DdrO: insight into the metalloprotease/repressor-controlled radiation response in Deinococcus. Nucleic Acids Res. 47, 11403–11417 (2019).
pubmed: 31598697
pmcid: 6868357
Blanchard, L. et al. Conservation and diversity of the IrrE/DdrO-controlled radiation response in radiation-resistant Deinococcus bacteria. MicrobiologyOpen 6, e00477 (2017).
pubmed: 28397370
pmcid: 5552922
Lu, H. Z. & Hua, Y. J. PprI: The key protein in response to DNA damage in Deinococcus. Front. Cell Dev. Biol. 8, 609714 (2021).
pubmed: 33537302
pmcid: 7848106
Maret, W. Zinc coordination environments in proteins as redox sensors and signal transducers. Antioxid. Redox Signal 8, 1419–1441 (2006).
pubmed: 16987000
Kroncke, K. D. & Klotz, L. O. Zinc fingers as biologic redox switches? Antioxid. Redox Signal 11, 1015–1027 (2009).
pubmed: 19132878
Ciccia, A. & Elledge, S. J. The DNA damage response: making it safe to play with knives. Mol. Cell 40, 179–204 (2010).
pubmed: 20965415
pmcid: 2988877
Devigne, A. et al. DdrO is an essential protein that regulates the radiation desiccation response and the apoptotic-like cell death in the radioresistant Deinococcus radiodurans bacterium. Mol. Microbiol. 96, 1069–1084 (2015).
pubmed: 25754115
Vujicic-Zagar, A. et al. Crystal structure of the IrrE protein, a central regulator of DNA damage repair in deinococcaceae. J. Mol. Biol. 386, 704–716 (2009).
pubmed: 19150362
Matthews, B. W., Ohlendorf, D. H., Anderson, W. F. & Takeda, Y. Structure of the DNA-BINDING REGION OF LAC REPRESSOR INFERRED FROM ITS HOMOLOGY WITH CRO REPRESSor. P Natl Acad. Sci.-Biol. 79, 1428–1432 (1982).
Wintjens, R. & Rooman, M. Structural classification of HTH DNA-binding domains and protein-DNA interaction modes. J. Mol. Biol. 262, 294–313 (1996).
pubmed: 8831795
Vidal-Eychenie, S., Decaillet, C., Basbous, J. & Constantinou, A. DNA structure-specific priming of ATR activation by DNA-PKcs. J. Cell Biol. 202, 421–429 (2013).
pubmed: 23897887
pmcid: 3734074
Martensson, S. & Hammarsten, O. DNA-dependent protein kinase catalytic subunit. Structural requirements for kinase activation by DNA ends. J. Biol. Chem. 277, 3020–3029 (2002).
pubmed: 11700303
Lau, R. K., Enustun, E., Gu, Y., Nguyen, J. V. & Corbett, K. D. A conserved signaling pathway activates bacterial CBASS immune signaling in response to DNA damage. EMBO J. 41, e111540 (2022).
pubmed: 36156805
pmcid: 9670203
Magerand, R., Rey, P., Blanchard, L. & de Groot, A. Redox signaling through zinc activates the radiation response in Deinococcus bacteria. Sci. Rep. 11, 4528 (2021).
pubmed: 33633226
pmcid: 7907104
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
pubmed: 34265844
pmcid: 8371605
Evans R., et al. Protein complex prediction with AlphaFold-Multimer. Preprint at bioRxiv https://doi.org/10.1101/2021.10.04.463034 (2021).
Chowell, D. et al. Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy. Science 359, 582 (2018).
pubmed: 29217585
Ahmed, R. et al. A Public BCR present in a unique dual-receptor-expressing lymphocyte from Type 1 diabetes patients encodes a potent T cell autoantigen. Cell 177, 1583 (2019).
pubmed: 31150624
pmcid: 7962621
Bell, D. R. et al. In silico design and validation of high-affinity RNA aptamers targeting epithelial cellular adhesion molecule dimers. Proc. Natl Acad. Sci. USA 117, 8486–8493 (2020).
pubmed: 32234785
pmcid: 7165443
Zhu, Q. et al. O-GlcNAcylation promotes pancreatic tumor growth by regulating malate dehydrogenase 1. Nat. Chem. Biol. 18, 1087 (2022).
pubmed: 35879546
Song, Y. et al. A mutagenesis study of autoantigen optimization for potential T1D vaccine design. Proc. Natl Acad. Sci. USA 120, e2214430120 (2023).
pubmed: 37040399
pmcid: 10120010
Zhou, R. H., Das, P. & Royyuru, A. K. Single mutation induced H3N2 Hemagglutinin antibody neutralization: A free energy perturbation study. J. Phys. Chem. B 112, 15813–15820 (2008).
pubmed: 19367871
Das, P., Li, J. Y., Royyuru, A. K. & Zhou, R. H. Free energy simulations reveal a double mutant Avian H5N1 Virus Hemagglutinin with altered receptor binding specificity. J. Comput Chem. 30, 1654–1663 (2009).
pubmed: 19399777
Zhang, D. et al. Mutagenesis and structural studies reveal the basis for the specific binding of SARS-CoV-2 SL3 RNA element with human TIA1 protein. Nat. Commun. 14, 3715 (2023).
pubmed: 37349329
pmcid: 10287707
Krissinel, E. & Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774–797 (2007).
pubmed: 17681537
Kim, J. I. & Cox, M. M. The RecA proteins of Deinococcus radiodurans and Escherichia coli promote DNA strand exchange via inverse pathways. Proc. Natl Acad. Sci. USA 99, 7917–7921 (2002).
pubmed: 12048253
pmcid: 122995
Daly, M. J. et al. Accumulation of Mn(II) in Deinococcus radiodurans facilitates gamma-radiation resistance. Science 306, 1025–1028 (2004).
pubmed: 15459345
Borsetti, F. et al. Manganese is a Deinococcus radiodurans growth limiting factor in rich culture medium. Microbiology 164, 1266–1275 (2018).
pubmed: 30052171
Chen, Z., Tang, Y., Hua, Y. & Zhao, Y. Structural features and functional implications of proteins enabling the robustness of Deinococcus radiodurans. Comput. Struct. Biotechnol. J. 18, 2810–2817 (2020).
pubmed: 33133422
pmcid: 7575645
Cejka, P. & Symington, L. S. DNA end resection: mechanism and control. Annu. Rev. Genet. 55, 285–307 (2021).
pubmed: 34813349
Ngo, G. H., Balakrishnan, L., Dubarry, M., Campbell, J. L. & Lydall, D. The 9-1-1 checkpoint clamp stimulates DNA resection by Dna2-Sgs1 and Exo1. Nucleic Acids Res. 42, 10516–10528 (2014).
pubmed: 25122752
pmcid: 4176354
Wigley, D. B. Bacterial DNA repair: recent insights into the mechanism of RecBCD, AddAB and AdnAB. Nat. Rev. Microbiol. 11, 9–13 (2013).
pubmed: 23202527
Cheng, K. Y. et al. Structural basis for DNA 5 ‘-end resection by RecJ. Elife 5, e14294 (2016).
pubmed: 27058167
pmcid: 4846377
Blackwood, J. K. et al. Structural and functional insights into DNA-end processing by the archaeal HerA helicase-NurA nuclease complex. Nucleic Acids Res. 40, 3183–3196 (2012).
pubmed: 22135300
Xu, Y. et al. Mechanisms of helicase activated DNA end resection in bacteria. Structure 30, 1298–1306.e3 (2022).
pubmed: 35841886
Cheng, K. et al. A Novel C-terminal domain of RecJ is critical for interaction with HerA in Deinococcus radiodurans. Front. Microbiol. 6, 1302 (2015).
pubmed: 26648913
pmcid: 4663267
Zahradka, K. et al. Reassembly of shattered chromosomes in Deinococcus radiodurans. Nature 443, 569–573 (2006).
pubmed: 17006450
Heikaus, C. C., Pandit, J. & Klevit, R. E. Cyclic nucleotide binding GAF domains from phosphodiesterases: structural and mechanistic insights. Structure 17, 1551–1557 (2009).
pubmed: 20004158
pmcid: 2801740
Martinez, S. E., Beavo, J. A. & Hol, W. G. GAF domains: two-billion-year-old molecular switches that bind cyclic nucleotides. Mol. Inter. 2, 317–323 (2002).
Gao, B. et al. Structural basis for regulation of SOS response in bacteria. Proc. Natl Acad. Sci. USA 120, e2217493120 (2023).
pubmed: 36598938
pmcid: 9926225
Gao, G. J., Lu, H. M., Huang, L. F. & Hua, Y. J. Construction of DNA damage response gene pprI function-deficient and function-complementary mutants in Deinococcus radiodurans. Chin. Sci. Bull. 50, 311–316 (2005).
Zhou, C. et al. Probing the sORF-encoded peptides of Deinococcus radiodurans in response to extreme stress. Mol. Cell. Proteom. 21, 100423 (2022).
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D. 66, 213–221 (2010).
pubmed: 20124702
pmcid: 2815670
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. Sect. D.-Biol. Crystallogr. 66, 486–501 (2010).
Dai, J. L. et al. Late embryogenesis abundant group3 protein (DrLEA3) is involved in antioxidation in the extremophilic bacterium Deinococcus radiodurans. Microbiol. Res. 240, 126559 (2020).
pubmed: 32721821
Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W. & Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79, 926–935 (1983).
Abraham, M. J. et al. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1-2, 19–25 (2015).
Lindorff-Larsen, K. et al. Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins 78, 1950–1958 (2010).
pubmed: 20408171
pmcid: 2970904
Ivani, I. et al. Parmbsc1: a refined force field for DNA simulations. Nat. Methods 13, 55–58 (2016).
pubmed: 26569599
Li, P., Roberts, B. P., Chakravorty, D. K. & Merz, K. M. Jr Rational Design of particle mesh Ewald compatible Lennard-Jones parameters for +2 Metal cations in explicit solvent. J. Chem. Theory Comput. 9, 2733–2748 (2013).
pubmed: 23914143
pmcid: 3728907
Bussi, G., Donadio, D. & Parrinello, M. Canonical sampling through velocity rescaling. J. Chem. Phys. 126, 014101 (2007).
pubmed: 17212484
Parrinello, M. & Rahman, A. Polymorphic transitions in single crystals: A new molecular dynamics method. J. Appl. Phys. 52, 7182–7190 (1981).
Darden, T., York, D. & Pedersen, L. Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems. J. Chem. Phys. 98, 10089–10092 (1993).
Hess, B., Bekker, H., Berendsen, H. J. C. & Fraaije, J. G. E. M. LINCS: A linear constraint solver for molecular simulations. J. Comput. Chem. 18, 1463–1472 (1997).
Humphrey, W., Dalke, A. & Schulten, K. VMD: visual molecular dynamics. J. Mol. Graph. 14, 33–38 (1996).
pubmed: 8744570
Jiang, W. & Roux, B. Free Energy Perturbation Hamiltonian Replica-Exchange Molecular Dynamics (FEP/H-REMD) for absolute ligand binding free energy calculations. J. Chem. Theory Comput. 6, 2559–2565 (2010).
pubmed: 21857813
pmcid: 3157700
Seeliger, D. & de Groot, B. L. Protein thermostability calculations using alchemical free energy simulations. Biophys. J. 98, 2309–2316 (2010).
pubmed: 20483340
pmcid: 2872215
Gapsys, V., Michielssens, S., Seeliger, D. & de Groot, B. L. pmx: Automated protein structure and topology generation for alchemical perturbations. J. Comput. Chem. 36, 348–354 (2015).
pubmed: 25487359
Beutler, T. C., Mark, A. E., Vanschaik, R. C., Gerber, P. R. & Vangunsteren, W. F. Avoiding singularities and numerical instabilities in free-energy calculations based on molecular simulations. Chem. Phys. Lett. 222, 529–539 (1994).
Shirts, M. R. & Chodera, J. D. Statistically optimal analysis of samples from multiple equilibrium states. J. Chem. Phys. 129, 124105 (2008).
pubmed: 19045004
pmcid: 2671659
Klimovich, P. V., Shirts, M. R. & Mobley, D. L. Guidelines for the analysis of free energy calculations. J. Comput. Aided Mol. Des. 29, 397–411 (2015).
pubmed: 25808134
pmcid: 4420631