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8d7h

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Cryo-EM structure of human CLCF1 in complex with CRLF1 and CNTFR alpha

Structural highlights

8d7h 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 3.4Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CNTFR_HUMAN Binds to CNTF. The alpha subunit provides the receptor specificity.

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^[1]

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

References

↑ 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