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Structural insights into the assembly of gp130 family cytokine signaling complexes.

Authors :
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
Source :
Science advances [Sci Adv] 2023 Mar 15; Vol. 9 (11), pp. eade4395. Date of Electronic Publication: 2023 Mar 17.
Publication Year :
2023

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.

Details

Language :
English
ISSN :
2375-2548
Volume :
9
Issue :
11
Database :
MEDLINE
Journal :
Science advances
Publication Type :
Academic Journal
Accession number :
36930708
Full Text :
https://doi.org/10.1126/sciadv.ade4395