3dlq

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Crystal structure of the IL-22/IL-22R1 complex

Structural highlights

3dlq is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.9Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

I22R1_HUMAN Component of the receptor for IL20, IL22 and IL24. Component of IL22 receptor formed by IL22RA1 and IL10RB enabling IL22 signaling via JAK/STAT pathways. IL22 also induces activation of MAPK1/MAPK3 and Akt kinases pathways. Component of one of the receptor for IL20 and IL24 formed by IL22RA1 and IL20RB also signaling through STATs activation. Mediates IL24 antiangiogenic activity as well as IL24 inhibitory effect on endothelial cell tube formation and differentiation.[1] [2] [3] [4] [5] [6]

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-22 (IL-22) is a member of the interleukin-10 cytokine family, which is involved in anti-microbial defenses, tissue damage protection and repair, and acute phase responses. Its signaling mechanism involves the sequential binding of IL-22 to interleukin-22 receptor 1 (IL-22R1), and of this dimer to interleukin-10 receptor 2 (IL-10R2) extracellular domain. We report a 1.9A crystal structure of the IL-22/IL-22R1 complex, revealing crucial interacting residues at the IL-22/IL-22R1 interface. Functional importance of key residues was confirmed by site-directed mutagenesis and functional studies. Based on the X-ray structure of the binary complex, we discuss a molecular basis of the IL-22/IL-22R1 recognition by IL-10R2.

Crystal structure of the IL-22/IL-22R1 complex and its implications for the IL-22 signaling mechanism.,Bleicher L, de Moura PR, Watanabe L, Colau D, Dumoutier L, Renauld JC, Polikarpov I FEBS Lett. 2008 Sep 3;582(20):2985-92. Epub 2008 Aug 7. PMID:18675809[7]

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

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See Also

References

  1. ↑ Kotenko SV, Izotova LS, Mirochnitchenko OV, Esterova E, Dickensheets H, Donnelly RP, Pestka S. Identification of the functional interleukin-22 (IL-22) receptor complex: the IL-10R2 chain (IL-10Rbeta ) is a common chain of both the IL-10 and IL-22 (IL-10-related T cell-derived inducible factor, IL-TIF) receptor complexes. J Biol Chem. 2001 Jan 26;276(4):2725-32. Epub 2000 Oct 16. PMID:11035029 doi:http://dx.doi.org/10.1074/jbc.M007837200
  2. ↑ Dumoutier L, Leemans C, Lejeune D, Kotenko SV, Renauld JC. Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types. J Immunol. 2001 Oct 1;167(7):3545-9. PMID:11564763
  3. ↑ Wang M, Tan Z, Zhang R, Kotenko SV, Liang P. Interleukin 24 (MDA-7/MOB-5) signals through two heterodimeric receptors, IL-22R1/IL-20R2 and IL-20R1/IL-20R2. J Biol Chem. 2002 Mar 1;277(9):7341-7. Epub 2001 Nov 12. PMID:11706020 doi:http://dx.doi.org/10.1074/jbc.M106043200
  4. ↑ Parrish-Novak J, Xu W, Brender T, Yao L, Jones C, West J, Brandt C, Jelinek L, Madden K, McKernan PA, Foster DC, Jaspers S, Chandrasekher YA. Interleukins 19, 20, and 24 signal through two distinct receptor complexes. Differences in receptor-ligand interactions mediate unique biological functions. J Biol Chem. 2002 Dec 6;277(49):47517-23. Epub 2002 Sep 25. PMID:12351624 doi:http://dx.doi.org/10.1074/jbc.M205114200
  5. ↑ Ramesh R, Mhashilkar AM, Tanaka F, Saito Y, Branch CD, Sieger K, Mumm JB, Stewart AL, Boquoi A, Dumoutier L, Grimm EA, Renauld JC, Kotenko S, Chada S. Melanoma differentiation-associated gene 7/interleukin (IL)-24 is a novel ligand that regulates angiogenesis via the IL-22 receptor. Cancer Res. 2003 Aug 15;63(16):5105-13. PMID:12941841
  6. ↑ Brand S, Dambacher J, Beigel F, Zitzmann K, Heeg MH, Weiss TS, Prufer T, Olszak T, Steib CJ, Storr M, Goke B, Diepolder H, Bilzer M, Thasler WE, Auernhammer CJ. IL-22-mediated liver cell regeneration is abrogated by SOCS-1/3 overexpression in vitro. Am J Physiol Gastrointest Liver Physiol. 2007 Apr;292(4):G1019-28. Epub, 2007 Jan 4. PMID:17204547 doi:http://dx.doi.org/00239.2006
  7. ↑ Bleicher L, de Moura PR, Watanabe L, Colau D, Dumoutier L, Renauld JC, Polikarpov I. Crystal structure of the IL-22/IL-22R1 complex and its implications for the IL-22 signaling mechanism. FEBS Lett. 2008 Sep 3;582(20):2985-92. Epub 2008 Aug 7. PMID:18675809 doi:10.1016/j.febslet.2008.07.046

Contents


PDB ID 3dlq

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