Interleukin-22 forms dimers that are recognized by two interleukin-22R1 receptor chains.
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.
de Oliveira Neto
Mario
M
Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, Brasil.
Ferreira
José Ribamar
JR
Colau
Didier
D
Fischer
Hannes
H
Nascimento
Alessandro S
AS
Craievich
Aldo F
AF
Dumoutier
Laure
L
Renauld
Jean-Christophe
JC
Polikarpov
Igor
I
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
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