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. Author manuscript; available in PMC: 2023 Mar 20.
Published in final edited form as: Chem Rev. 2022 Jun 17;122(17):13952–13988. doi: 10.1021/acs.chemrev.1c01035

Figure 10.

Figure 10.

Overall structure of IL-10Rα and IL-10Rβ complex in apo or IL-10 bound states and the proposed activation mechanism. Receptors IL-10Rα (blue) and IL-10Rβ (green) are shown in cartoon representations, whereas the ligand IL-10 is shown as surface representations with semi-transparency. The missing domains (TM and TIR) in each structure are shown as schematic representations.

A) Crystal structures of IL-10Rα and IL-10Rβ in their respective apo states as inactive monomers (PDBs: 1Y6K and 3LQM). The ECDs of both proteins consist of D1 and D2 domains. IL-10Rα has a longer ICD than IL-10Rβ, both contains two regions (named Box1 and Box2) that interact with the JAK1 or Tyk2 kinases.

B) Cryo-EM structure of 2:2:2 IL-10/IL-10Rα/IL-10Rβ in two different views (PDB: 6X93). Dimerization of IL-10Rα/IL-10Rβ induced by IL-10 leads to engagement of JAK1 and Tyk2 kinases, and phosphorylation of JAK1 and Tyk2 as well as the ICDs of IL-10Rα and IL-10Rβ.