Structural organization of a full-length gp130/LIF-R cytokine receptor transmembrane complex
By G. Skiniotis, P. Lupardus, M. Martick, Thomas Walz, K. Garcia. 2008
112 citations recorded by the source corpus.
Summary gp130 is a shared receptor for at least nine cytokines, and can signal either as a homodimer, or as a heterodimer with Leukemia Inhibitory Factor Receptor (LIF-R). Here we biophysically and structurally characterize the full-length, transmembrane form of a quaternary cytokine receptor complex consisting of gp130, LIF-R, the cytokine Ciliary Neurotrophic Factor (CNTF), and its alpha receptor (CNTF-Rα). Thermodynamic analysis indicates that, unlike the cooperative assembly of the symmetric gp130/Interleukin-6/IL-6Rα hexameric complex, CNTF/CNTF-Rα heterodimerizes gp130 and LIF-R via non-cooperative energetics to form an asymmetric 1:1:1:1 complex. Single particle electron microscopic (EM) analysis of the full-length gp130/LIF-R/CNTF-Rα/CNTF quaternary complex elucidates an asymmetric structural arrangement, in which the receptor extracellular and transmembrane segments join as a continuous, rigid unit, poised to sensitively transduce ligand engagement to the membrane-proximal intracellular signaling regions. These studies also enumerate the organizing principles for assembly of the ‘tall’ class of gp130-family cytokine receptor complexes including LIF, IL-27, IL-12, and others.
Subfields: Molecular Biology, Oncology, Radiology, Nuclear Medicine and Imaging
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Citations in the corpus
- The composition and signaling of the IL-35 receptor are unconventional (2012, background): “However, additional molecules might facilitate cytokine binding or downstream signaling, although this would be unprecedented in the IL-6R and IL-12R familie”
- Structural insights into the assembly and activation of the IL‐27 signaling complex (2022, unknown): “Protein purification was carried out using the method described in Spangler et al (2019).”