Acknowledgement
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2021R1C1C100396112 and 2018R1A6A1A0302560722) and the Yonsei University Research Fund of 2021 (2021-22-0050).
References
- Hershko A and Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67, 425-479 https://doi.org/10.1146/annurev.biochem.67.1.425
- Mann M and Jensen ON (2003) Proteomic analysis of posttranslational modifications. Nat Biotechnol 21, 255-261 https://doi.org/10.1038/nbt0303-255
- Olsen JV and Mann M (2013) Status of large-scale analysis of post-translational modifications by mass spectrometry. Mol Cell Proteomics 12, 3444-3452 https://doi.org/10.1074/mcp.O113.034181
- Goldstein G, Scheid M, Hammerling U, Schlesinger DH, Niall HD and Boyse EA (1975) Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells. Proc Natl Acad Sci U S A 72, 11-15 https://doi.org/10.1073/pnas.72.1.11
- Yau R and Rape M (2016) The increasing complexity of the ubiquitin code. Nat Cell Biol 18, 579-586 https://doi.org/10.1038/ncb3358
- Gerlach B, Cordier SM, Schmukle AC et al (2011) Linear ubiquitination prevents inflammation and regulates immune signalling. Nature 471, 591-596 https://doi.org/10.1038/nature09816
- Ikeda F, Rahighi S, Wakatsuki S and Dikic I (2011) Selective binding of linear ubiquitin chains to NEMO in NF-kappaB activation. Adv Exp Med Biol 691, 107-114 https://doi.org/10.1007/978-1-4419-6612-4_11
- Kirisako T, Kamei K, Murata S et al (2006) A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J 25, 4877-4887 https://doi.org/10.1038/sj.emboj.7601360
- Tokunaga F, Sakata S, Saeki Y et al (2009) Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation. Nat Cell Biol 11, 123-132 https://doi.org/10.1038/ncb1821
- Walczak H, Iwai K and Dikic I (2012) Generation and physiological roles of linear ubiquitin chains. BMC Biol 10, 23 https://doi.org/10.1186/1741-7007-10-23
- Morris JR and Solomon E (2004) BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Hum Mol Genet 13, 807-817 https://doi.org/10.1093/hmg/ddh095
- Nishikawa H, Ooka S, Sato K et al (2004) Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase. J Biol Chem 279, 3916-3924 https://doi.org/10.1074/jbc.M308540200
- Ordureau A, Sarraf SA, Duda DM et al (2014) Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis. Mol Cell 56, 360-375 https://doi.org/10.1016/j.molcel.2014.09.007
- Braten O, Livneh I, Ziv T et al (2016) Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination. Proc Natl Acad Sci U S A 113, E4639-E4647
- Chau V, Tobias JW, Bachmair A et al (1989) A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science 243, 1576-1583 https://doi.org/10.1126/science.2538923
- Gregori L, Poosch MS, Cousins G and Chau V (1990) A uniform isopeptide-linked multiubiquitin chain is sufficient to target substrate for degradation in ubiquitin-mediated proteolysis. J Biol Chem 265, 8354-8357 https://doi.org/10.1016/S0021-9258(19)38890-8
- Shabek N, Herman-Bachinsky Y, Buchsbaum S et al (2012) The size of the proteasomal substrate determines whether its degradation will be mediated by mono- or polyubiquitylation. Mol Cell 48, 87-97 https://doi.org/10.1016/j.molcel.2012.07.011
- Gatti M, Pinato S, Maiolica A et al (2015) RNF168 promotes noncanonical K27 ubiquitination to signal DNA damage. Cell Rep 10, 226-238 https://doi.org/10.1016/j.celrep.2014.12.021
- Clevers H and Nusse R (2012) Wnt/beta-catenin signaling and disease. Cell 149, 1192-1205 https://doi.org/10.1016/j.cell.2012.05.012
- Fei C, Li Z, Li C et al (2013) Smurf1-mediated Lys29-linked nonproteolytic polyubiquitination of axin negatively regulates Wnt/beta-catenin signaling. Mol Cell Biol 33, 4095-4105 https://doi.org/10.1128/MCB.00418-13
- Al-Hakim AK, Zagorska A, Chapman L, Deak M, Peggie M and Alessi DR (2008) Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-linked polyubiquitin chains. Biochem J 411, 249-260 https://doi.org/10.1042/BJ20080067
- Huang H, Jeon MS, Liao L et al (2010) K33-linked polyubiquitination of T cell receptor-zeta regulates proteolysis-independent T cell signaling. Immunity 33, 60-70 https://doi.org/10.1016/j.immuni.2010.07.002
- Thrower JS, Hoffman L, Rechsteiner M and Pickart CM (2000) Recognition of the polyubiquitin proteolytic signal. EMBO J 19, 94-102 https://doi.org/10.1093/emboj/19.1.94
- Duncan LM, Piper S, Dodd RB et al (2006) Lysine-63-linked ubiquitination is required for endolysosomal degradation of class I molecules. EMBO J 25, 1635-1645 https://doi.org/10.1038/sj.emboj.7601056
- Hofmann RM and Pickart CM (1999) Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell 96, 645-653 https://doi.org/10.1016/S0092-8674(00)80575-9
- Oeckinghaus A, Wegener E, Welteke V et al (2007) Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation. EMBO J 26, 4634-4645 https://doi.org/10.1038/sj.emboj.7601897
- Ni X, Kou W, Gu J et al (2019) TRAF6 directs FOXP3 localization and facilitates regulatory T-cell function through K63-linked ubiquitination. EMBO J 38, e99766 https://doi.org/10.15252/embj.201899766
- Wang J, Yang S, Liu L, Wang H and Yang B (2017) HTLV-1 Tax impairs K63-linked ubiquitination of STING to evade host innate immunity. Virus Res 232, 13-21 https://doi.org/10.1016/j.virusres.2017.01.016
- Husnjak K and Dikic I (2012) Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions. Annu Rev Biochem 81, 291-322 https://doi.org/10.1146/annurev-biochem-051810-094654
- Schulman BA and Harper JW (2009) Ubiquitin-like protein activation by E1 enzymes: the apex for downstream signalling pathways. Nat Rev Mol Cell Biol 10, 319-331 https://doi.org/10.1038/nrm2673
- Olsen SK and Lima CD (2013) Structure of a ubiquitin E1-E2 complex: insights to E1-E2 thioester transfer. Mol Cell 49, 884-896 https://doi.org/10.1016/j.molcel.2013.01.013
- Ye Y and Rape M (2009) Building ubiquitin chains: E2 enzymes at work. Nat Rev Mol Cell Biol 10, 755-764 https://doi.org/10.1038/nrm2780
- Buetow L and Huang DT (2016) Structural insights into the catalysis and regulation of E3 ubiquitin ligases. Nat Rev Mol Cell Biol 17, 626-642 https://doi.org/10.1038/nrm.2016.91
- Deshaies RJ and Joazeiro CA (2009) RING domain E3 ubiquitin ligases. Annu Rev Biochem 78, 399-434 https://doi.org/10.1146/annurev.biochem.78.101807.093809
- Berndsen CE and Wolberger C (2014) New insights into ubiquitin E3 ligase mechanism. Nat Struct Mol Biol 21, 301-307 https://doi.org/10.1038/nsmb.2780
- Lorick KL, Jensen JP, Fang S, Ong AM, Hatakeyama S and Weissman AM (1999) RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc Natl Acad Sci U S A 96, 11364-11369 https://doi.org/10.1073/pnas.96.20.11364
- Ohi MD, Vander Kooi CW, Rosenberg JA, Chazin WJ and Gould KL (2003) Structural insights into the U-box, a domain associated with multi-ubiquitination. Nat Struct Biol 10, 250-255 https://doi.org/10.1038/nsb906
- Marin I and Ferrus A (2002) Comparative genomics of the RBR family, including the Parkinson's disease-related gene parkin and the genes of the ariadne subfamily. Mol Biol Evol 19, 2039-2050 https://doi.org/10.1093/oxfordjournals.molbev.a004029
- Spratt DE, Walden H and Shaw GS (2014) RBR E3 ubiquitin ligases: new structures, new insights, new questions. Biochem J 458, 421-437 https://doi.org/10.1042/BJ20140006
- Kwasna D, Abdul Rehman SA, Natarajan J et al (2018) Discovery and characterization of ZUFSP/ZUP1, a distinct deubiquitinase class important for genome stability. Mol Cell 70, 150-164 e156 https://doi.org/10.1016/j.molcel.2018.02.023
- Reyes-Turcu FE, Ventii KH and Wilkinson KD (2009) Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Annu Rev Biochem 78, 363-397 https://doi.org/10.1146/annurev.biochem.78.082307.091526
- Fields BS, Benson RF and Besser RE (2002) Legionella and Legionnaires' disease: 25 years of investigation. Clin Microbiol Rev 15, 506-526 https://doi.org/10.1128/CMR.15.3.506-526.2002
- Ashida H, Kim M and Sasakawa C (2014) Exploitation of the host ubiquitin system by human bacterial pathogens. Nat Rev Microbiol 12, 399-413 https://doi.org/10.1038/nrmicro3259
- Choy A, Dancourt J, Mugo B et al (2012) The Legionella effector RavZ inhibits host autophagy through irreversible Atg8 deconjugation. Science 338, 1072-1076 https://doi.org/10.1126/science.1227026
- Liu Y, Mukherjee R, Bonn F et al (2021) Serine-ubiquitination regulates Golgi morphology and the secretory pathway upon Legionella infection. Cell Death Differ 28, 2957-2969 https://doi.org/10.1038/s41418-021-00830-y
- Shin D, Mukherjee R, Liu Y et al (2020) Regulation of phosphoribosyl-linked serine ubiquitination by deubiquitinases DupA and DupB. Mol Cell 77, 164-179 e166 https://doi.org/10.1016/j.molcel.2019.10.019
- Wan M, Wang X, Huang C et al (2019) A bacterial effector deubiquitinase specifically hydrolyses linear ubiquitin chains to inhibit host inflammatory signalling. Nat Microbiol 4, 1282-1293 https://doi.org/10.1038/s41564-019-0454-1
- Ensminger AW and Isberg RR (2010) E3 ubiquitin ligase activity and targeting of BAT3 by multiple Legionella pneumophila translocated substrates. Infect Immun 78, 3905-3919 https://doi.org/10.1128/IAI.00344-10
- Price CT, Al-Khodor S, Al-Quadan T et al (2009) Molecular mimicry by an F-box effector of Legionella pneumophila hijacks a conserved polyubiquitination machinery within macrophages and protozoa. PLoS Pathog 5, e1000704 https://doi.org/10.1371/journal.ppat.1000704
- Miyamoto K and Saito K (2018) Concise machinery for monitoring ubiquitination activities using novel artificial RING fingers. Protein Sci 27, 1354-1363 https://doi.org/10.1002/pro.3427
- Kubori T, Hyakutake A and Nagai H (2008) Legionella translocates an E3 ubiquitin ligase that has multiple U-boxes with distinct functions. Mol Microbiol 67, 1307-1319 https://doi.org/10.1111/j.1365-2958.2008.06124.x
- Kubori T, Shinzawa N, Kanuka H and Nagai H (2010) Legionella metaeffector exploits host proteasome to temporally regulate cognate effector. PLoS Pathog 6, e1001216 https://doi.org/10.1371/journal.ppat.1001216
- Quaile AT, Urbanus ML, Stogios PJ et al (2015) Molecular characterization of LubX: functional divergence of the u-box fold by Legionella pneumophila. Structure 23, 1459-1469 https://doi.org/10.1016/j.str.2015.05.020
- Benirschke RC, Thompson JR, Nomine Y et al (2010) Molecular basis for the association of human E4B U box ubiquitin ligase with E2-conjugating enzymes UbcH5c and Ubc4. Structure 18, 955-965 https://doi.org/10.1016/j.str.2010.04.017
- Mevissen TET and Komander D (2017) Mechanisms of deubiquitinase specificity and regulation. Annu Rev Biochem 86, 159-192 https://doi.org/10.1146/annurev-biochem-061516-044916
- Edelmann MJ, Iphofer A, Akutsu M et al (2009) Structural basis and specificity of human otubain 1-mediated deubiquitination. Biochem J 418, 379-390 https://doi.org/10.1042/BJ20081318
- Keusekotten K, Elliott PR, Glockner L et al (2013) OTULIN antagonizes LUBAC signaling by specifically hydrolyzing Met1-linked polyubiquitin. Cell 153, 1312-1326 https://doi.org/10.1016/j.cell.2013.05.014
- Mevissen TE, Hospenthal MK, Geurink PP et al (2013) OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis. Cell 154, 169-184 https://doi.org/10.1016/j.cell.2013.05.046
- Kitao T, Nagai H and Kubori T (2020) Divergence of Legionella effectors reversing conventional and unconventional ubiquitination. Front Cell Infect Microbiol 10, 448 https://doi.org/10.3389/fcimb.2020.00448
- Shin D, Bhattacharya A, Cheng YL et al (2020) Bacterial OTU deubiquitinases regulate substrate ubiquitination upon Legionella infection. Elife 9, e58277 https://doi.org/10.7554/eLife.58277
- Takekawa N, Kubori T, Iwai T, Nagai H and Imada K (2022) Structural basis of ubiquitin recognition by a bacterial ovarian tumor deubiquitinase LotA. J Bacteriol 204, e0037621 https://doi.org/10.1128/JB.00376-21
- Kitao T, Taguchi K, Seto S et al (2020) Legionella manipulates non-canonical SNARE pairing using a bacterial deubiquitinase. Cell Rep 32, 108107 https://doi.org/10.1016/j.celrep.2020.108107
- Ma K, Zhen X, Zhou B et al (2020) The bacterial deubiquitinase Ceg23 regulates the association of Lys-63-linked polyubiquitin molecules on the Legionella phagosome. J Biol Chem 295, 1646-1657 https://doi.org/10.1074/jbc.ra119.011758
- Schubert AF, Nguyen JV, Franklin TG et al (2020) Identification and characterization of diverse OTU deubiquitinases in bacteria. EMBO J 39, e105127 https://doi.org/10.15252/embj.2020105127
- Schulze-Niemand E, Naumann M and Stein M (2021) The activation and selectivity of the Legionella RavD deubiquitinase. Front Mol Biosci 8, 770320 https://doi.org/10.3389/fmolb.2021.770320
- Schulze-Niemand E, Naumann M and Stein M (2022) Substrate-assisted activation and selectivity of the bacterial RavD effector deubiquitinylase. Proteins 90, 947-958 https://doi.org/10.1002/prot.26286
- Qiu J, Sheedlo MJ, Yu K et al (2016) Ubiquitination independent of E1 and E2 enzymes by bacterial effectors. Nature 533, 120-124 https://doi.org/10.1038/nature17657
- Bhogaraju S, Kalayil S, Liu Y et al (2016) Phosphoribosylation of ubiquitin promotes serine ubiquitination and impairs conventional ubiquitination. Cell 167, 1636-1649 e1613 https://doi.org/10.1016/j.cell.2016.11.019
- Wan M, Sulpizio AG, Akturk A et al (2019) Deubiquitination of phosphoribosyl-ubiquitin conjugates by phosphodiesterase-domain-containing Legionella effectors. Proc Natl Acad Sci U S A 116, 23518-23526 https://doi.org/10.1073/pnas.1916287116
- Black MH, Osinski A, Gradowski M et al (2019) Bacterial pseudokinase catalyzes protein polyglutamylation to inhibit the SidE-family ubiquitin ligases. Science 364, 787-792 https://doi.org/10.1126/science.aaw7446
- Bhogaraju S, Bonn F, Mukherjee R et al (2019) Inhibition of bacterial ubiquitin ligases by SidJ-calmodulin catalysed glutamylation. Nature 572, 382-386 https://doi.org/10.1038/s41586-019-1440-8
- Song L, Xie Y, Li C et al (2021) The Legionella effector SdjA is a bifunctional enzyme that distinctly regulates phosphoribosyl ubiquitination. mBio 12, e0231621 https://doi.org/10.1128/mBio.02316-21
- Gan N, Zhen X, Liu Y et al (2019) Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase. Nature 572, 387-391 https://doi.org/10.1038/s41586-019-1439-1
- Osinski A, Black MH, Pawlowski K, Chen Z, Li Y and Tagliabracci VS (2021) Structural and mechanistic basis for protein glutamylation by the kinase fold. Mol Cell 81, 4527-4539 e4528 https://doi.org/10.1016/j.molcel.2021.08.007
- Adams M, Sharma R, Colby T, Weis F, Matic I and Bhogaraju S (2021) Structural basis for protein glutamylation by the Legionella pseudokinase SidJ. Nat Commun 12, 6174 https://doi.org/10.1038/s41467-021-26429-y
- Akturk A, Wasilko DJ, Wu X et al (2018) Mechanism of phosphoribosyl-ubiquitination mediated by a single Legionella effector. Nature 557, 729-733 https://doi.org/10.1038/s41586-018-0147-6
- Dong Y, Mu Y, Xie Y et al (2018) Structural basis of ubiquitin modification by the Legionella effector SdeA. Nature 557, 674-678 https://doi.org/10.1038/s41586-018-0146-7
- Kalayil S, Bhogaraju S, Bonn F et al (2018) Insights into catalysis and function of phosphoribosyl-linked serine ubiquitination. Nature 557, 734-738 https://doi.org/10.1038/s41586-018-0145-8
- Wang Y, Shi M, Feng H et al (2018) Structural insights into non-canonical ubiquitination catalyzed by SidE. Cell 173, 1231-1243 e1216 https://doi.org/10.1016/j.cell.2018.04.023
- Prokhorova E, Zobel F, Smith R et al (2021) Serine-linked PARP1 auto-modification controls PARP inhibitor response. Nat Commun 12, 4055 https://doi.org/10.1038/s41467-021-24361-9
- Valleau D, Quaile AT, Cui H et al (2018) Discovery of ubiquitin deamidases in the pathogenic arsenal of Legionella pneumophila. Cell Rep 23, 568-583 https://doi.org/10.1016/j.celrep.2018.03.060
- Puvar K, Iyer S, Fu J et al (2020) Legionella effector MavC targets the Ube2N-Ub conjugate for noncanonical ubiquitination. Nat Commun 11, 2365 https://doi.org/10.1038/s41467-020-16211-x
- Guan H, Fu J, Yu T et al (2020) Molecular basis of ubiquitination catalyzed by the bacterial transglutaminase MavC. Adv Sci (Weinh) 7, 2000871 https://doi.org/10.1002/advs.202000871
- Gan N, Guan H, Huang Y et al (2020) Legionella pneumophila regulates the activity of UBE2N by deamidase-mediated deubiquitination. EMBO J 39, e102806 https://doi.org/10.15252/embj.2019102806
- Mu Y, Wang Y, Huang Y et al (2020) Structural insights into the mechanism and inhibition of transglutaminase-induced ubiquitination by the Legionella effector MavC. Nat Commun 11, 1774 https://doi.org/10.1038/s41467-020-15645-7