Structural insights into the assembly and activation of IL-1β with its receptors.
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.
Wang
Dongli
D
Center for Structural Biology, School of Life Sciences, Ministry of Education Key Laboratory of Bioinformatics, Tsinghua University, Beijing, China.
Zhang
Senyan
S
Li
Liang
L
Liu
Xi
X
Mei
Kunrong
K
Wang
Xinquan
X
D000595:Amino Acid Sequence; D003461:Crystallography; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000737:chemistry; D053577:Interleukin-1 Receptor Accessory Protein / Q000737:chemistry* / Q000378:metabolism; D053583:Interleukin-1beta / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D053574:Receptors, Interleukin-1 Type II / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction
D053590:Interleukin 1 Receptor Antagonist Protein; D053577:Interleukin-1 Receptor Accessory Protein; D053583:Interleukin-1beta; D053574:Receptors, Interleukin-1 Type II
Nat Protoc. 2007;2(11):2728-33
18007608
Trends Immunol. 2001 Oct;22(10):536-7
11574262
Acta Crystallogr D Biol Crystallogr. 2002 Oct;58(Pt 10 Pt 2):1772-9
12351820
Ann N Y Acad Sci. 2009 Dec;1182:111-23
20074280
FEBS Lett. 1998 Jun 16;429(3):299-302
9662436
Eur J Immunol. 2010 Mar;40(3):599-606
20201008
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
15572765
Annu Rev Immunol. 2009;27:29-60
18817510
J Biol Chem. 2009 Sep 4;284(36):24478-89
19553661
J Biol Chem. 1995 Sep 22;270(38):22460-6
7673234
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
19461840
Nat Rev Immunol. 2010 Feb;10(2):89-102
20081871
Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20711-5
19104048
J Immunol. 1998 Dec 15;161(12):6871-7
9862719
Clin Exp Immunol. 2007 Aug;149(2):217-25
17590166
Proc Natl Acad Sci U S A. 1989 Dec;86(24):9667-71
2602367
Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3
15299374
Structure. 2009 Oct 14;17(10):1398-410
19836339
Sci STKE. 2003 Feb 25;2003(171):re3
12606705
Clin Exp Rheumatol. 2002 Sep-Oct;20(5 Suppl 27):S1-13
14989423
Nature. 1984 Nov 29-Dec 5;312(5993):458-62
6209582
Immunol Today. 1994 Dec;15(12):562-6
7848516
J Biol Chem. 2000 Nov 24;275(47):36927-33
10903327
J Immunol. 1998 Nov 15;161(10):5614-20
9820540
J Biol Chem. 1997 Oct 10;272(41):25737-42
9325300
J Biol Chem. 1998 Nov 6;273(45):29445-50
9792649
Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1190-5
10655506
Immunity. 2003 Jan;18(1):87-96
12530978
Blood. 1996 Mar 15;87(6):2095-147
8630372
Proc Natl Acad Sci U S A. 1984 Dec;81(24):7907-11
6083565
Nat Rev Drug Discov. 2004 Apr;3(4):330-9
15060528
Arthritis Rheum. 2005 Jul;52(7):1960-7
15986340
Front Biosci. 1996 Oct 01;1:d270-308
9159234
Science. 1988 Jul 29;241(4865):585-9
2969618
Nature. 1997 Mar 13;386(6621):194-200
9062194
Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2658-62
1826365
Science. 1993 Jul 23;261(5120):472-5
8332913
Cytokine. 1994 Mar;6(2):206-14
8032002
Vitam Horm. 2006;74:229-54
17027517
Nature. 1985 Jun 20-26;315(6021):641-7
2989698
Protein Eng. 1992 Mar;5(2):171-6
1594572
Acta Crystallogr D Biol Crystallogr. 2002 Nov;58(Pt 11):1948-54
12393927
EMBO J. 1991 Oct;10(10):2821-32
1833184
J Immunol. 1998 Apr 1;160(7):3170-9
9531272
FEBS Lett. 2001 Jun 15;499(1-2):65-8
11418113
Nat Struct Biol. 2003 Nov;10(11):966-71
14528293
Eur Cytokine Netw. 1997 Jun;8(2):161-71
9262965
Proc Natl Acad Sci U S A. 2006 May 23;103(21):8060-5
16690741
J Biol Chem. 2002 Mar 29;277(13):10998-1003
11790772
Eur J Immunol. 1997 Jan;27(1):262-7
9022028
Annu Rev Immunol. 2009;27:519-50
19302047
Nature. 1997 Mar 13;386(6621):190-4
9062193
J Biol Chem. 1995 Jun 9;270(23):13757-65
7775431