2h24 | pdb_00002h24
Crystal structure of human IL-10
Structural highlights
Function[IL10_HUMAN] Inhibits the synthesis of a number of cytokines, including IFN-gamma, IL-2, IL-3, TNF and GM-CSF produced by activated macrophages and by helper T-cells. 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 PubMedInterleukin-10 receptor 2 (IL-10R2) is a critical component of the IL-10.IL-10R1.IL-10R2 complex which regulates IL-10-mediated immunomodulatory responses. The ternary IL-10 signaling complex is assembled in a sequential order with the IL-10.IL-10R1 interaction occurring first followed by engagement of the IL-10R2 chain. In this study we map the IL-10R2 binding site on IL-10 using surface plasmon resonance and cell-based assays. Critical IL-10R2 binding residues are located in helix A adjacent to the previously identified IL-10R1 recognition surface. Interestingly, IL-10R2 binding residues located in the N-terminal end of helix A exhibit large structural differences between unbound cIL-10 and cIL-10.IL-10R1 crystal structures. This suggests IL-10R1-induced conformational changes regulate IL-10R2 binding and assembly of the ternary IL-10.IL-10R1.IL-10R2 complex. The basic mechanistic features of the assembly process are likely shared by six additional class-2 cytokines (viral IL-10s, IL-22, IL-26, IL-28A, IL28B, and IL-29) to promote IL-10R2 binding to six additional receptor complexes. These studies highlight the importance of structure in regulating low affinity protein-protein interactions and IL-10 signal transduction. Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex.,Yoon SI, Logsdon NJ, Sheikh F, Donnelly RP, Walter MR J Biol Chem. 2006 Nov 17;281(46):35088-96. Epub 2006 Sep 18. PMID:16982608[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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