title: Interleukin-22 forms dimers that are recognized by two interleukin-22R1 receptor chains.
abstract: Interleukin-22 (IL-22) is a class 2 cytokine whose primary structure is similar to that of interleukin 10 (IL-10) and interferon-gamma (IFN-gamma). 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.
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, Brasil.
authors.forename: Mario
authors.initials: M
authors.lastname: de Oliveira Neto
authors.forename: José Ribamar
authors.initials: JR
authors.lastname: Ferreira
authors.forename: Didier
authors.initials: D
authors.lastname: Colau
authors.forename: Hannes
authors.initials: H
authors.lastname: Fischer
authors.forename: Alessandro S
authors.initials: AS
authors.lastname: Nascimento
authors.forename: Aldo F
authors.initials: AF
authors.lastname: Craievich
authors.forename: Laure
authors.initials: L
authors.lastname: Dumoutier
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
authors.forename: Igor
authors.initials: I
authors.lastname: Polikarpov
mesh_terms: D000595:Amino Acid Sequence; D003432:Cross-Linking Reagents / Q000737:chemistry; D016207:Cytokines / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D004586:Electrophoresis; D005976:Glutaral / Q000737:chemistry; D006801:Humans; D016753:Interleukin-10 / Q000737:chemistry / Q000378:metabolism; D007378:Interleukins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D018123:Receptors, Interleukin / Q000737:chemistry* / Q000378:metabolism; D012542:Scattering, Radiation; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction; D000097043:Interleukin-22
chemical_list: D003432:Cross-Linking Reagents; D016207:Cytokines; D005976:Glutaral; D016753:Interleukin-10; D007378:Interleukins; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C415369:interleukin-22 receptor