Interleukin-22 forms dimers that are recognized by two interleukin-22R1 receptor chains |
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Authors: | de Oliveira Neto Mario Ferreira José Ribamar Colau Didier Fischer Hannes Nascimento Alessandro S Craievich Aldo F Dumoutier Laure Renauld Jean-Christophe Polikarpov Igor |
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Institution: | * Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, Brasil † Ludwig Institute for Cancer Research, Brussels Branch and the Experimental Medicine Unit, Christian de Duve Institute of Cellular Pathology, Université de Louvain, Brussels, Belgium ‡ Instituto de Física, Universidade de São Paulo, São Paulo, Brasil |
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Abstract: | Interleukin-22 (IL-22) is a class 2 cytokine whose primary structure is similar to that of interleukin 10 (IL-10) and interferon-γ (IFN-γ). IL-22 induction during acute phase immune response indicates its involvement in mechanisms of inflammation. Structurally different from IL-10 and a number of other members of IL-10 family, which form intertwined inseparable V-shaped dimers of two identical polypeptide chains, a single polypeptide chain of IL-22 folds on itself in a relatively globular structure. Here we present evidence, based on native gel electrophoresis, glutaraldehyde cross-linking, dynamic light scattering, and small angle x-ray scattering experiments, that human IL-22 forms dimers and tetramers in solution under protein concentrations assessable by these experiments. Unexpectedly, low-resolution molecular shape of IL-22 dimers is strikingly similar to that of IL-10 and other intertwined cytokine dimeric forms. Furthermore, we determine an ab initio molecular shape of the IL-22/IL-22R1 complex which reveals the V-shaped IL-22 dimer interacting with two cognate IL-22R1 molecules. Based on this collective evidence, we argue that dimerization might be a common mechanism of all class 2 cytokines for the molecular recognition with their respective membrane receptor. We also speculate that the IL-22 tetramer formation could represent a way to store the cytokine in nonactive form at high concentrations that could be readily converted into functionally active monomers and dimers upon interaction with the cognate cellular receptors. |
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