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Structure paper

TitleStructural insights into the assembly of gp130 family cytokine signaling complexes.
Journal, issue, pagesSci Adv, Vol. 9, Issue 11, Page eade4395, Year 2023
Publish dateMar 15, 2023
AuthorsYi Zhou / Panayiotis E Stevis / Jing Cao / Kei Saotome / Jiaxi Wu / Arielle Glatman Zaretsky / Sokol Haxhinasto / George D Yancopoulos / Andrew J Murphy / Mark W Sleeman / William C Olson / Matthew C Franklin /
PubMed AbstractThe 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. ...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.
External linksSci Adv / PubMed:36930708 / PubMed Central
MethodsEM (single particle)
Resolution2.93 - 4.14 Å
Structure data

27221

8d6a

EMDB-27221: Cryo-EM map of human LIF signaling complex with full extracellular domains
PDB-8d6a: Cryo-EM structure of human LIF signaling complex: model containing the interaction core region
Method: EM (single particle) / Resolution: 3.54 Å

27227

8d74

EMDB-27227: Cryo-EM map of human CNTF signaling complex with full extracellular domains: refined from selected full particle dataset, with better resolution in the interaction core region
PDB-8d74: Cryo-EM structure of human CNTF signaling complex: model containing the interaction core region
Method: EM (single particle) / Resolution: 3.03 Å

27228

8d7e

EMDB-27228, PDB-8d7e:
Cryo-EM structure of human CNTFR alpha in complex with the Fab fragments of two antibodies
Method: EM (single particle) / Resolution: 2.93 Å

EMDB-27229: Cryo-EM map of human CNTF signaling complex with full extracellular domains: refined from a particle subset, with lower global resolution but improved LIFR D6-D8 density
Method: EM (single particle) / Resolution: 3.37 Å

27230

8d7h

EMDB-27230, PDB-8d7h:
Cryo-EM structure of human CLCF1 in complex with CRLF1 and CNTFR alpha
Method: EM (single particle) / Resolution: 3.4 Å

27231

8d7r

EMDB-27231: Cryo-EM map of human CLCF1 signaling complex with full extracellular domains
PDB-8d7r: Cryo-EM structure of human CLCF1 signaling complex: model containing the interaction core region
Method: EM (single particle) / Resolution: 3.9 Å

27244

8d82

EMDB-27244: Cryo-EM map of detergent-solubilized human IL-6 signaling complex with full extracellular domains
PDB-8d82: Cryo-EM structure of human IL-6 signaling complex in detergent: model containing full extracellular domains
Method: EM (single particle) / Resolution: 3.22 Å

EMDB-27246: Cryo-EM map of human IL-27 signaling complex with full extracellular domains
Method: EM (single particle) / Resolution: 4.14 Å

27247

8d85

EMDB-27247: Cryo-EM map of human IL-27 signaling complex: focused refinement on the interaction core region
PDB-8d85: Cryo-EM structure of human IL-27 signaling complex: model containing the interaction core region
Method: EM (single particle) / Resolution: 3.81 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
KeywordsCYTOKINE / cytokine signaling / LIF / gp130 / LIFR / CNTF / CNTFR alpha / CYTOKINE/Immune System / antibody / Fab / CYTOKINE-Immune System complex / CLCF1 / CRLF1 / IL-6 / IL-6R alpha / IL-27 / IL-27R alpha / EBI3 / p28

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