3o4o

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Crystal structure of an Interleukin-1 receptor complexCrystal structure of an Interleukin-1 receptor complex

Structural highlights

3o4o is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IL1B_HUMAN] Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.[1] [IL1AP_HUMAN] Coreceptor with IL1R1. Associates with IL1R1 bound to IL1B to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependent activation of NF-kappa-B and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. Recruits TOLLIP to the signaling complex. Does not bind to interleukin-1 alone; binding of IL1RN to IL1R1, prevents its association with IL1R1 to form a signaling complex. The cellular response is modulated through a non-signaling association with the membrane IL1R2 decoy receptor. Secreted forms (isoforms 2 and 3) associate with secreted ligand-bound IL1R2 and increase the affinity of secreted IL1R2 for IL1B; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors.[2] [3] [4] [IL1R2_HUMAN] Non-signaling receptor for IL1A, IL1B and IL1RN. Reduces IL1B activities. Serves as a decoy receptor by competetive binding to IL1B and preventing its binding to IL1R1. Also modulates cellular response through non-signaling association with IL1RAP after binding to IL1B. IL1R2 (membrane and secreted forms) preferentially binds IL1B and poorly IL1A and IL1RN. The secreted IL1R2 recruits secreted IL1RAP with high affinity; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors.[5] [6] [7] [8]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Interleukin 1beta (IL-1beta) 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-1beta-IL-1RI to form the signaling-competent complex remains elusive. Here we present the crystal structure of IL-1beta bound to IL-1 receptor type II (IL-1RII) and IL-1RAcP. IL-1beta-IL-1RII generated a composite binding surface to recruit IL-1RAcP. Biochemical analysis demonstrated that IL-1beta-IL-1RI and IL-1beta-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.

Structural insights into the assembly and activation of IL-1beta with its receptors.,Wang D, Zhang S, Li L, Liu X, Mei K, Wang X Nat Immunol. 2010 Aug 29. PMID:20802483[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Van Damme J, De Ley M, Opdenakker G, Billiau A, De Somer P, Van Beeumen J. Homogeneous interferon-inducing 22K factor is related to endogenous pyrogen and interleukin-1. Nature. 1985 Mar 21-27;314(6008):266-8. PMID:3920526
  2. ↑ Huang J, Gao X, Li S, Cao Z. Recruitment of IRAK to the interleukin 1 receptor complex requires interleukin 1 receptor accessory protein. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12829-32. PMID:9371760
  3. ↑ Jensen LE, Muzio M, Mantovani A, Whitehead AS. IL-1 signaling cascade in liver cells and the involvement of a soluble form of the IL-1 receptor accessory protein. J Immunol. 2000 May 15;164(10):5277-86. PMID:10799889
  4. ↑ Smith DE, Hanna R, Della Friend, Moore H, Chen H, Farese AM, MacVittie TJ, Virca GD, Sims JE. The soluble form of IL-1 receptor accessory protein enhances the ability of soluble type II IL-1 receptor to inhibit IL-1 action. Immunity. 2003 Jan;18(1):87-96. PMID:12530978
  5. ↑ Neumann D, Kollewe C, Martin MU, Boraschi D. The membrane form of the type II IL-1 receptor accounts for inhibitory function. J Immunol. 2000 Sep 15;165(6):3350-7. PMID:10975853
  6. ↑ Smith DE, Hanna R, Della Friend, Moore H, Chen H, Farese AM, MacVittie TJ, Virca GD, Sims JE. The soluble form of IL-1 receptor accessory protein enhances the ability of soluble type II IL-1 receptor to inhibit IL-1 action. Immunity. 2003 Jan;18(1):87-96. PMID:12530978
  7. ↑ Giri JG, Wells J, Dower SK, McCall CE, Guzman RN, Slack J, Bird TA, Shanebeck K, Grabstein KH, Sims JE, et al.. Elevated levels of shed type II IL-1 receptor in sepsis. Potential role for type II receptor in regulation of IL-1 responses. J Immunol. 1994 Dec 15;153(12):5802-9. PMID:7989776
  8. ↑ Lang D, Knop J, Wesche H, Raffetseder U, Kurrle R, Boraschi D, Martin MU. 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 Dec 15;161(12):6871-7. PMID:9862719
  9. ↑ Wang D, Zhang S, Li L, Liu X, Mei K, Wang X. Structural insights into the assembly and activation of IL-1beta with its receptors. Nat Immunol. 2010 Aug 29. PMID:20802483 doi:10.1038/ni.1925

3o4o, resolution 3.30Å

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