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8d82

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

Structural highlights

8d82 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.22Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IL6RA_HUMAN Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal. Signal activation necessitate an association with IL6ST. Activation may lead to the regulation of the immune response, acute-phase reactions and hematopoiesis.^[1] ^[2] Low concentration of a soluble form of IL6 receptor acts as an agonist of IL6 activity.^[3] ^[4]

Publication Abstract from PubMed

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.

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Martens AS, Bode JG, Heinrich PC, Graeve L. The cytoplasmic domain of the interleukin-6 receptor gp80 mediates its basolateral sorting in polarized madin-darby canine kidney cells. J Cell Sci. 2000 Oct;113 ( Pt 20):3593-602. PMID:11017875
↑ Buk DM, Renner O, Graeve L. Increased association with detergent-resistant membranes/lipid rafts of apically targeted mutants of the interleukin-6 receptor gp80. Eur J Cell Biol. 2005 Oct;84(10):819-31. PMID:16270750
↑ Martens AS, Bode JG, Heinrich PC, Graeve L. The cytoplasmic domain of the interleukin-6 receptor gp80 mediates its basolateral sorting in polarized madin-darby canine kidney cells. J Cell Sci. 2000 Oct;113 ( Pt 20):3593-602. PMID:11017875
↑ Buk DM, Renner O, Graeve L. Increased association with detergent-resistant membranes/lipid rafts of apically targeted mutants of the interleukin-6 receptor gp80. Eur J Cell Biol. 2005 Oct;84(10):819-31. PMID:16270750
↑ 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. Structural insights into the assembly of gp130 family cytokine signaling complexes. Sci Adv. 2023 Mar 15;9(11):eade4395. PMID:36930708 doi:10.1126/sciadv.ade4395