Structural Insights into the Assembly and Activation of IL-1β with Its Receptors

Overview

Journal Nat Immunol

Date 2010 Aug 31

PMID 20802483

Citations 81

Authors

Dongli Wang

Senyan Zhang

Liang Li

Xi Liu

Kunrong Mei

Xinquan Wang

Affiliations

Soon will be listed here.

Abstract

Interleukin 1β (IL-1β) is a key orchestrator of inflammation and host defense that exerts its effects through IL-1 receptor type I (IL-1RI) and IL-1 receptor accessory protein (IL-1RAcP). How IL-1RAcP is recruited by IL-1β-IL-1RI to form the signaling-competent complex remains elusive. Here we present the crystal structure of IL-1β bound to IL-1 receptor type II (IL-1RII) and IL-1RAcP. IL-1β-IL-1RII generated a composite binding surface to recruit IL-1RAcP. Biochemical analysis demonstrated that IL-1β-IL-1RI and IL-1β-IL-1RII interacted similarly with IL-1RAcP. It also showed the importance of two loops of IL-1 receptor antagonist (IL-1Ra) in determining its antagonism. Our results provide a structural basis for assembly and activation of the IL-1 receptor and offer a general cytokine-receptor architecture that governs the IL-1 family of cytokines.

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References

Brunger A . Version 1.2 of the Crystallography and NMR system. Nat Protoc. 2007; 2(11):2728-33. DOI: 10.1038/nprot.2007.406. View

Sims J, Nicklin M, Bazan J, Barton J, Busfield S, Ford J . A new nomenclature for IL-1-family genes. Trends Immunol. 2001; 22(10):536-7. DOI: 10.1016/s1471-4906(01)02040-3. View

Schneider T, Sheldrick G . Substructure solution with SHELXD. Acta Crystallogr D Biol Crystallogr. 2002; 58(Pt 10 Pt 2):1772-9. DOI: 10.1107/s0907444902011678. View

Goldbach-Mansky R . Blocking interleukin-1 in rheumatic diseases. Ann N Y Acad Sci. 2010; 1182:111-23. PMC: 3080043. DOI: 10.1111/j.1749-6632.2009.05159.x. View

Malinowsky D, Lundkvist J, Laye S, Bartfai T . Interleukin-1 receptor accessory protein interacts with the type II interleukin-1 receptor. FEBS Lett. 1998; 429(3):299-302. DOI: 10.1016/s0014-5793(98)00467-0. View

Dinarello C . IL-1: discoveries, controversies and future directions. Eur J Immunol. 2010; 40(3):599-606. DOI: 10.1002/eji.201040319. View

Emsley P, Cowtan K . Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr. 2004; 60(Pt 12 Pt 1):2126-32. DOI: 10.1107/S0907444904019158. View

Wang X, Lupardus P, LaPorte S, Garcia K . Structural biology of shared cytokine receptors. Annu Rev Immunol. 2008; 27:29-60. PMC: 3981547. DOI: 10.1146/annurev.immunol.24.021605.090616. View

Argiriadi M, Xiang T, Wu C, Ghayur T, Borhani D . Unusual water-mediated antigenic recognition of the proinflammatory cytokine interleukin-18. J Biol Chem. 2009; 284(36):24478-89. PMC: 2782040. DOI: 10.1074/jbc.M109.023887. View

10.

Greenfeder S, Varnell T, Powers G, SHUSTER D, McIntyre K, Ryan D . Insertion of a structural domain of interleukin (IL)-1 beta confers agonist activity to the IL-1 receptor antagonist. Implications for IL-1 bioactivity. J Biol Chem. 1995; 270(38):22460-6. DOI: 10.1074/jbc.270.38.22460. View

11.

McCoy A, Grosse-Kunstleve R, Adams P, Winn M, Storoni L, Read R . Phaser crystallographic software. J Appl Crystallogr. 2009; 40(Pt 4):658-674. PMC: 2483472. DOI: 10.1107/S0021889807021206. View

12.

Sims J, Smith D . The IL-1 family: regulators of immunity. Nat Rev Immunol. 2010; 10(2):89-102. DOI: 10.1038/nri2691. View

13.

Krumm B, Meng X, Li Y, Xiang Y, Deng J . Structural basis for antagonism of human interleukin 18 by poxvirus interleukin 18-binding protein. Proc Natl Acad Sci U S A. 2008; 105(52):20711-5. PMC: 2634891. DOI: 10.1073/pnas.0809086106. View

14.

Lang D, Knop J, Wesche H, Raffetseder U, Kurrle R, Boraschi D . The type II IL-1 receptor interacts with the IL-1 receptor accessory protein: a novel mechanism of regulation of IL-1 responsiveness. J Immunol. 1998; 161(12):6871-7. View

15.

Barksby H, Lea S, Preshaw P, Taylor J . The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders. Clin Exp Immunol. 2007; 149(2):217-25. PMC: 1941943. DOI: 10.1111/j.1365-2249.2007.03441.x. View

16.

Priestle J, Schar H, Grutter M . Crystallographic refinement of interleukin 1 beta at 2.0 A resolution. Proc Natl Acad Sci U S A. 1989; 86(24):9667-71. PMC: 298562. DOI: 10.1073/pnas.86.24.9667. View

17.

. The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr. 1994; 50(Pt 5):760-3. DOI: 10.1107/S0907444994003112. View

18.

Lingel A, Weiss T, Niebuhr M, Pan B, Appleton B, Wiesmann C . Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors--insight into heterotrimeric IL-1 signaling complexes. Structure. 2009; 17(10):1398-410. PMC: 2766095. DOI: 10.1016/j.str.2009.08.009. View

19.

Dunne A, ONeill L . The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci STKE. 2003; 2003(171):re3. DOI: 10.1126/stke.2003.171.re3. View

20.

Dinarello C . The IL-1 family and inflammatory diseases. Clin Exp Rheumatol. 2004; 20(5 Suppl 27):S1-13. View