8d74
From Proteopedia
Cryo-EM structure of human CNTF signaling complex: model containing the interaction core region
Structural highlights
FunctionIL6RB_HUMAN Signal-transducing molecule. The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize gp130 for initiating signal transmission. Binds to IL6/IL6R (alpha chain) complex, resulting in the formation of high-affinity IL6 binding sites, and transduces the signal. Does not bind IL6. May have a role in embryonic development (By similarity). The type I OSM receptor is capable of transducing OSM-specific signaling events. Publication Abstract from PubMedThe 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. Structural insights into the assembly of gp130 family cytokine signaling complexes.,Zhou Y, Stevis PE, Cao J, Saotome K, Wu J, Glatman Zaretsky A, Haxhinasto S, Yancopoulos GD, Murphy AJ, Sleeman MW, Olson WC, Franklin MC Sci Adv. 2023 Mar 15;9(11):eade4395. doi: 10.1126/sciadv.ade4395. Epub 2023 Mar , 17. PMID:36930708[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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