1. Structural Organization of a Full-Length gp130/LIF-R Cytokine Receptor Transmembrane Complex
- Author
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Skiniotis, Georgios, Lupardus, Patrick J., Martick, Monika, Walz, Thomas, and Garcia, K. Christopher
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CYTOKINES , *CELLULAR immunity , *IMMUNOREGULATION , *CHEMOKINES - Abstract
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 noncooperative energetics to form an asymmetric 1:1:1:1 complex. Single particle electron microscopic 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. [Copyright &y& Elsevier]
- Published
- 2008
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