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Production of Disulfide-stabilized Transmembrane Peptide Complexes for Structural Studies
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Published on: March 6, 2013

Structural organization of a full-length gp130/LIF-R cytokine receptor transmembrane complex

Georgios Skiniotis1, Patrick J Lupardus, Monika Martick

  • 1Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.

Molecular Cell
|September 9, 2008
PubMed

Insights

This study reveals how Ciliary Neurotrophic Factor (CNTF) assembles an asymmetric receptor complex with gp130 and Leukemia Inhibitory Factor Receptor (LIF-R). This structural insight clarifies signaling for a key class of cytokine receptors.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Cellular Signaling

Background:

  • gp130 is a crucial receptor for numerous cytokines, mediating signaling through homodimer or heterodimer formation with LIF-R.
  • Understanding the assembly and structure of these quaternary complexes is vital for deciphering cytokine-mediated cellular responses.

Purpose of the Study:

  • To biophysically and structurally characterize the full-length transmembrane receptor complex formed by gp130, LIF-R, CNTF, and CNTF-Ralpha.
  • To elucidate the assembly principles governing the "tall" class of gp130 family cytokine receptor complexes.

Main Methods:

  • Thermodynamic analysis to determine the energetics of complex assembly.
  • Single particle electron microscopy to resolve the structural arrangement of the quaternary complex.

Main Results:

  • CNTF/CNTF-Ralpha forms an asymmetric 1:1:1:1 complex by heterodimerizing gp130 and LIF-R through noncooperative energetics.
  • Electron microscopy revealed a continuous, rigid unit formed by the receptor extracellular and transmembrane segments, poised for signal transduction.
  • Established organizing principles for the assembly of "tall" gp130 family cytokine receptor complexes.

Conclusions:

  • The asymmetric assembly and structure of the CNTF receptor complex are critical for its function.
  • These findings provide a framework for understanding the assembly and signaling mechanisms of related "tall" cytokine receptor families.

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