8D82

Cryo-EM structure of human IL-6 signaling complex in detergent: model containing full extracellular domains

Summary for 8D82

• Entry DOI: 10.2210/pdb8d82/pdb
• EMDB information: 27244
• Descriptor: Soluble interleukin-6 receptor subunit alpha, Interleukin-6, Interleukin-6 receptor subunit beta, ... (5 entities in total)
• Functional Keywords: cytokine signaling, il-6, il-6r alpha, gp130, cytokine
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 281460.18

Authors

Zhou, Y.,Franklin, M.C. (deposition date: 2022-06-07, release date: 2023-03-29)

Primary citation

Zhou, Y.,Stevis, P.E.,Cao, J.,Saotome, K.,Wu, J.,Glatman Zaretsky, A.,Haxhinasto, S.,Yancopoulos, G.D.,Murphy, A.J.,Sleeman, M.W.,Olson, W.C.,Franklin, M.C.
Structural insights into the assembly of gp130 family cytokine signaling complexes.
Sci Adv, 9:eade4395-eade4395, 2023

PubMed Abstract: 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.

PubMed: 36930708
DOI: 10.1126/sciadv.ade4395

Experimental method

ELECTRON MICROSCOPY (3.22 Å)