Structure of IL-22/IL-22R1Structure of IL-22/IL-22R1
Structural highlights
3dgc is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[IL22_HUMAN] Cytokine that contributes to the inflammatory response in vivo. [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
IL-22 is an IL-10 family cytokine that initiates innate immune responses against bacterial pathogens and contributes to immune disease. IL-22 biological activity is initiated by binding to a cell-surface complex composed of IL-22R1 and IL-10R2 receptor chains and further regulated by interactions with a soluble binding protein, IL-22BP, which shares sequence similarity with an extracellular region of IL-22R1 (sIL-22R1). IL-22R1 also pairs with the IL-20R2 chain to induce IL-20 and IL-24 signaling. To define the molecular basis of these diverse interactions, we have determined the structure of the IL-22/sIL-22R1 complex. The structure, combined with homology modeling and surface plasmon resonance studies, defines the molecular basis for the distinct affinities and specificities of IL-22 and IL-10 receptor chains that regulate cellular targeting and signal transduction to elicit effective immune responses.
Structure of IL-22 bound to its high-affinity IL-22R1 chain.,Jones BC, Logsdon NJ, Walter MR Structure. 2008 Sep 10;16(9):1333-44. Epub 2008 Jul 3. PMID:18599299[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑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
↑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
↑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
↑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
↑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
↑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
↑Jones BC, Logsdon NJ, Walter MR. Structure of IL-22 bound to its high-affinity IL-22R1 chain. Structure. 2008 Sep 10;16(9):1333-44. Epub 2008 Jul 3. PMID:18599299 doi:http://dx.doi.org/10.1016/j.str.2008.06.005
