Structural insights into the assembly of gp130 family cytokine signaling complexes

Sci Adv. 2023 Mar 15;9(11):eade4395. doi: 10.1126/sciadv.ade4395. Epub 2023 Mar 17.


The interleukin-6 (IL-6) family cytokines signal through gp130 receptor homodimerization or heterodimerization with a second signaling receptor and play crucial roles in various cellular processes. We determined cryo-electron microscopy structures of five signaling complexes of this family, containing full receptor ectodomains bound to their respective ligands ciliary neurotrophic factor, cardiotrophin-like cytokine factor 1 (CLCF1), leukemia inhibitory factor, IL-27, and IL-6. Our structures collectively reveal similarities and differences in the assembly of these complexes. The acute bends at both signaling receptors in all complexes bring the membrane-proximal domains to a ~30 angstrom range but with distinct distances and orientations. We also reveal how CLCF1 engages its secretion chaperone cytokine receptor-like factor 1. Our data provide valuable insights for therapeutically targeting gp130-mediated signaling.

MeSH terms

  • Antigens, CD* / metabolism
  • Cryoelectron Microscopy
  • Cytokine Receptor gp130 / metabolism
  • Cytokines / metabolism
  • Interleukin-6* / metabolism
  • Leukemia Inhibitory Factor Receptor alpha Subunit / metabolism
  • Membrane Glycoproteins / metabolism


  • Cytokine Receptor gp130
  • Interleukin-6
  • Leukemia Inhibitory Factor Receptor alpha Subunit
  • Antigens, CD
  • Membrane Glycoproteins
  • Cytokines