8d85

From Proteopedia

Cryo-EM structure of human IL-27 signaling complex: model containing the interaction core region

Structural highlights

8d85 is a 4 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 3.81Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IL27B_HUMAN Associates with IL27 to form the IL-27 interleukin, a heterodimeric cytokine which functions in innate immunity. IL-27 has pro- and anti-inflammatory properties, that can regulate T-helper cell development, suppress T-cell proliferation, stimulate cytotoxic T-cell activity, induce isotype switching in B-cells, and that has diverse effects on innate immune cells. Among its target cells are CD4 T-helper cells which can differentiate in type 1 effector cells (TH1), type 2 effector cells (TH2) and IL17 producing helper T-cells (TH17). It drives rapid clonal expansion of naive but not memory CD4 T-cells. It also strongly synergizes with IL-12 to trigger interferon-gamma/IFN-gamma production of naive CD4 T-cells, binds to the cytokine receptor WSX-1/TCCR. Another important role of IL-27 is its antitumor activity as well as its antiangiogenic activity with activation of production of antiangiogenic chemokines.^[1]

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^[2]

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

References

↑ Pflanz S, Timans JC, Cheung J, Rosales R, Kanzler H, Gilbert J, Hibbert L, Churakova T, Travis M, Vaisberg E, Blumenschein WM, Mattson JD, Wagner JL, To W, Zurawski S, McClanahan TK, Gorman DM, Bazan JF, de Waal Malefyt R, Rennick D, Kastelein RA. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells. Immunity. 2002 Jun;16(6):779-90. doi: 10.1016/s1074-7613(02)00324-2. PMID:12121660 doi:http://dx.doi.org/10.1016/s1074-7613(02)00324-2
↑ 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