Skip to main content

1H, 13C, and 15N resonance assignments of the cytokine interleukin-36β isoform-2

Abstract

Interleukins are cytokines performing central tasks in the human immune system. Interleukin-36β (IL-36β) is a member of the interleukin-1 superfamily as are its homologues IL-36α and IL-36γ. All of them interact with a common receptor composed of IL-36R and IL-1R/acP. IL-36 cytokines can activate IL-36R to proliferation of CD4 + lymphocytes or stimulate M2 macrophages as potently as IL-1β. Within our efforts to study the structure–function relationship of the three interleukins IL-36α, IL-36β and IL-36γ by heteronuclear multidimensional NMR, we here report the 1H, 13C, and 15N resonance assignments for the backbone and side chain nuclei of cytokine interleukin-36β isoform-2.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Notes

  1. CCPNmr derived numbers for the γ/δ/ε-positions include aromatic residues for which currently no assignment was attempted.

References

  • Andersen NH, Neidigh JW, Harris SM, Lee GM, Liu Z, Tong H (1997) Extracting information from the temperature gradients of polypeptide NH chemical shifts. J Am Chem Soc 119:8547–8561

    Article  Google Scholar 

  • Bax A, Ikura M (1991) An efficient 3D NMR technique for correlating the proton and 15N backbone amide resonances with the alpha-carbon of the preceding residue in uniformly 15N/13C enriched proteins. J Biomol NMR 1:99–104

    Article  Google Scholar 

  • Bax A, Ikura M, Kay LE, Torchia DA, Tschudin R (1990) Comparison of different modes of two-dimensional reverse-correlation NMR for the study of proteins. J Magn Reson 86:304–318

    ADS  Google Scholar 

  • Blumberg H et al (2007) Opposing activities of two novel members of the IL-1 ligand family regulate skin inflammation. J Exp Med 204:2603–2614

    Article  Google Scholar 

  • Boehner A, Navarini AA, Eyerich K (2018) Generalized pustular psoriasis—a model disease for specific targeted immunotherapy, systematic review. Exp Dermatol 27:1067–1077

    Article  Google Scholar 

  • Cierpicki T, Otlewski J (2001) Amide proton temperature coefficients as hydrogen bond indicators in proteins. J Biomol NMR 21:249–261

    Article  Google Scholar 

  • Cierpicki T, Zhukov I, Byrd RA, Otlewski J (2002) Hydrogen bonds in human ubiquitin reflected in temperature coefficients of amide protons. J Magn Reson 157:178–180

    ADS  Article  Google Scholar 

  • Clancy DM, Henry CM, Davidovich PB, Sullivan GP, Belotcerkovskaya E, Martin SJ (2016) Production of biologically active IL-36 family cytokines through insertion of N-terminal caspase cleavage motifs. FEBS Open Bio 6:338–348

    Article  Google Scholar 

  • Clubb RT, Thanabal V, Wagner G (1992) A constant-time 3-Dimensional triple-resonance pulse scheme to correlate intraresidue H-1(N), N-15, and C-13′ chemical-shifts in N-15-C-13-labeled proteins. J Magn Reson 97:213–217

    ADS  Google Scholar 

  • Daley ME, Graether SP, Sykes BD (2004) Hydrogen bonding on the ice-binding face of a beta-helical antifreeze protein indicated by amide proton NMR chemical shifts. Biochemistry 43:13012–13017

    Article  Google Scholar 

  • Debets R et al (2001) Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor-related protein 2. J Immunol 167:1440–1446

    Article  Google Scholar 

  • Dunn EF, Gay NJ, Bristow AF, Gearing DP, O’Neill LA, Pei XY (2003) High-resolution structure of murine interleukin 1 homologue IL-1F5 reveals unique loop conformations for receptor binding specificity. Biochemistry 42:10938–10944

    Article  Google Scholar 

  • Farooq M et al (2013) Mutation analysis of the IL36RN gene in 14 Japanese patients with generalized pustular psoriasis. Hum Mutat 34:176–183

    Article  Google Scholar 

  • Gabay C, Towne JE (2015) Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions. J Leukoc Biol 97:645–652

    Article  Google Scholar 

  • Goradia N, Wissbrock A, Wiedemann C, Bordusa F, Ramachandran R, Imhof D, Ohlenschlager O (2016) (1)H, (13)C, and (15)N resonance assignments for the pro-inflammatory cytokine interleukin-36alpha. Biomol NMR Assign 10:329–333

    Article  Google Scholar 

  • Grzesiek S, Bax A (1993) Amino acid type determination in the sequential assignment procedure of uniformly 13C/15N-enriched proteins. J Biomol NMR 3:185–204

    Google Scholar 

  • Gunther S, Sundberg EJ (2014) Molecular determinants of agonist and antagonist signaling through the IL-36 receptor. J Immunol 193:921–930

    Article  Google Scholar 

  • Hafsa NE, Arndt D, Wishart DS (2015) CSI 3.0: a web server for identifying secondary and super-secondary structure in proteins using NMR chemical shifts. Nucleic Acids Res 43:W370–W377

    Article  Google Scholar 

  • Hahn M, Frey S, Hueber AJ (2017) The novel interleukin-1 cytokine family members in inflammatory diseases. Curr Opin Rheumatol 29:208–213

    Article  Google Scholar 

  • Henry CM, Sullivan GP, Clancy DM, Afonina IS, Kulms D, Martin SJ (2016) Neutrophil-Derived Proteases Escalate Inflammation through Activation of IL-36 Family Cytokines. Cell Rep 14:708–722

    Article  Google Scholar 

  • Kanazawa N, Nakamura T, Mikita N, Furukawa F (2013) Novel IL36RN mutation in a Japanese case of early onset generalized pustular psoriasis. J Dermatol 40:749–751

    Article  Google Scholar 

  • Kay LE, Ikura M, Tschudin R, Bax A (1990) 3-Dimensional triple-resonance NMR-spectroscopy of isotopically enriched proteins. J Magn Reson 89:496–514

    ADS  Google Scholar 

  • Kay LE, Guang-Yi X, Singer AU, Muhandiram DR, Forman-Kay JD (1993) A gradient-enhanced HCCH-TOCSY experiment for recording side-chain 1H and 13C correlations in H2O samples for proteins. J Magn Reson B 101:333–337

    ADS  Article  Google Scholar 

  • Kunz M, Ibrahim SM (2009) Cytokines and cytokine profiles in human autoimmune diseases and animal models of autoimmunity. Mediators Inflamm 2009:979258

    Article  Google Scholar 

  • Marrakchi S et al (2011) Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med 365:620–628

    Article  Google Scholar 

  • Moudgil KD, Choubey D (2011) Cytokines in autoimmunity: role in induction, regulation, and treatment. J Interferon Cytokine Res 31:695–703

    Article  Google Scholar 

  • O’Shea JJ, Ma A, Lipsky P (2002) Cytokines and autoimmunity. Nat Rev Immunol 2:37–45

    Article  Google Scholar 

  • Renert-Yuval Y, Horev L, Babay S, Tams S, Ramot Y, Zlotogorski A, Molho-Pessach V (2014) IL36RN mutation causing generalized pustular psoriasis in a Palestinian patient. Int J Dermatol 53:866–868

    Article  Google Scholar 

  • Schubert M, Labudde D, Oschkinat H, Schmieder P (2002) A software tool for the prediction of Xaa-Pro peptide bond conformations in proteins based on 13C chemical shift statistics. J Biomol NMR 24:149–154

    Article  Google Scholar 

  • Sims JE, Smith DE (2010) The IL-1 family: regulators of immunity. Nat Rev Immunol 10:89–102

    Article  Google Scholar 

  • Smith DE, Renshaw BR, Ketchem RR, Kubin M, Garka KE, Sims JE (2000) Four new members expand the interleukin-1 superfamily. J Biol Chem 275:1169–1175

    Article  Google Scholar 

  • Sugiura K, Takeichi T, Kono M, Ogawa Y, Shimoyama Y, Muro Y, Akiyama M (2012) A novel IL36RN/IL1F5 homozygous nonsense mutation, p.Arg10X, in a Japanese patient with adult-onset generalized pustular psoriasis. Br J Dermatol 167:699–701

    Article  Google Scholar 

  • Tauber M et al (2016) IL36RN mutations affect protein expression and function: a basis for genotype-phenotype correlation in pustular diseases. J Invest Dermatol 136:1811–1819

    Article  Google Scholar 

  • Towne JE, Sims JE (2012) IL-36 in psoriasis. Curr Opin Pharmacol 12:486–490

    Article  Google Scholar 

  • Towne JE, Garka KE, Renshaw BR, Virca GD, Sims JE (2004) Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs. J Biol Chem 279:13677–13688

    Article  Google Scholar 

  • Towne JE, Renshaw BR, Douangpanya J, Lipsky BP, Shen M, Gabel CA, Sims JE (2011) Interleukin-36 (IL-36) ligands require processing for full agonist (IL-36alpha, IL-36beta, and IL-36gamma) or antagonist (IL-36Ra) activity. J Biol Chem 286:42594–42602

    Article  Google Scholar 

  • Vranken WF et al (2005) The CCPN data model for NMR spectroscopy: development of a software pipeline. Proteins 59:687–696

    Article  Google Scholar 

  • Vuister GW, Bax A (1993) Quantitative J correlation—a new approach for measuring homonuclear 3-Bond J(H(N)H(Alpha) coupling-constants in N-15-enriched proteins. J Am Chem Soc 115:7772–7777

    Article  Google Scholar 

  • Wittekind M, Mueller L (1993) HNCACB: a high-sensitivity 3D NMR experiment to correlate amide proton and nitrogen resonances with the alpha-carbon and beta-carbon resonances in proteins. J Magn Reson B 101:201–205

    Article  Google Scholar 

Download references

Acknowledgements

Financial support by the Deutsche Forschungsgemeinschaft (DFG) within FOR 1738 (to D.I. and O.O.) is gratefully acknowledged. The FLI is a member of the Leibniz Association (WGL) and is financially supported by the Federal Government of Germany and the State of Thuringia. We thank Prof. Seamus Martin, Smurfit Institute of Genetics, Trinity College Dublin, Ireland for providing the IL-36β plasmid.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Oliver Ohlenschläger.

Additional information

In memory of Frank Große.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kumar, A., Wißbrock, A., Bellstedt, P. et al. 1H, 13C, and 15N resonance assignments of the cytokine interleukin-36β isoform-2. Biomol NMR Assign 13, 155–161 (2019). https://doi.org/10.1007/s12104-018-09869-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12104-018-09869-4

Keywords

  • Resonance assignments
  • Heteronuclear NMR
  • Interleukin-36β
  • Interleukin-1 superfamily
  • Cytokines