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-Structure paper
タイトル | Structural insights into the assembly of gp130 family cytokine signaling complexes. |
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ジャーナル・号・ページ | Sci Adv, Vol. 9, Issue 11, Page eade4395, Year 2023 |
掲載日 | 2023年3月15日 |
著者 | Yi 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 要旨 | 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. ...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. |
リンク | Sci Adv / PubMed:36930708 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.93 - 4.14 Å |
構造データ | EMDB-27221: Cryo-EM map of human LIF signaling complex with full extracellular domains 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 EMDB-27228, PDB-8d7e: 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 EMDB-27230, PDB-8d7h: EMDB-27231: Cryo-EM map of human CLCF1 signaling complex with full extracellular domains EMDB-27244: Cryo-EM map of detergent-solubilized human IL-6 signaling complex with full extracellular domains EMDB-27246: Cryo-EM map of human IL-27 signaling complex with full extracellular domains EMDB-27247: Cryo-EM map of human IL-27 signaling complex: focused refinement on the interaction core region |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | CYTOKINE / 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 |