8D74

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

8D74 の概要

• エントリーDOI: 10.2210/pdb8d74/pdb
• EMDBエントリー: 27227
• 分子名称: Interleukin-6 receptor subunit beta, Ciliary neurotrophic factor, Ciliary neurotrophic factor receptor subunit alpha, ... (6 entities in total)
• 機能のキーワード: cytokine signaling, cntf, cntfr alpha, gp130, lifr, cytokine
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 228501.83

構造登録者

Zhou, Y.,Franklin, M.C. (登録日: 2022-06-07, 公開日: 2023-03-29, 最終更新日: 2024-10-30)

主引用文献

Zhou, Y.,Stevis, P.E.,Cao, J.,Saotome, K.,Wu, J.,Glatman Zaretsky, A.,Haxhinasto, S.,Yancopoulos, G.D.,Murphy, A.J.,Sleeman, M.W.,Olson, W.C.,Franklin, M.C.
Structural insights into the assembly of gp130 family cytokine signaling complexes.
Sci Adv, 9:eade4395-eade4395, 2023

PubMed 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.

PubMed: 36930708
DOI: 10.1126/sciadv.ade4395

実験手法

ELECTRON MICROSCOPY (3.03 Å)