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Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling

Sung Il Yoon1, Naomi J Logsdon, Faruk Sheikh

  • 1Department of Microbiology and Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

The Journal of Biological Chemistry
|September 20, 2006
PubMed

Insights

Interleukin-10 receptor 2 (IL-10R2) binding to Interleukin-10 (IL-10) involves specific residues on helix A. IL-10R1 binding induces conformational changes, facilitating IL-10R2 engagement and ternary complex assembly.

Area of Science:

  • Immunology
  • Structural Biology
  • Molecular Biology

Background:

  • Interleukin-10 (IL-10) signaling is crucial for immunomodulation.
  • The IL-10.IL-10R1.IL-10R2 complex assembles sequentially, with IL-10R1 binding preceding IL-10R2.
  • Understanding the IL-10R2 binding mechanism is key to deciphering IL-10 signal transduction.

Purpose of the Study:

  • To map the IL-10 receptor 2 (IL-10R2) binding site on Interleukin-10 (IL-10).
  • To investigate the structural basis of IL-10R2 interaction with IL-10.
  • To elucidate the role of IL-10R1 in regulating IL-10R2 binding.

Main Methods:

  • Surface plasmon resonance (SPR) assays to measure binding kinetics.
  • Cell-based assays to confirm functional interactions.
  • Analysis of crystal structures of unbound and IL-10R1-bound IL-10.

Main Results:

  • Identified critical IL-10R2 binding residues located in helix A of IL-10.
  • Observed significant structural differences in helix A between unbound IL-10 and the IL-10.IL-10R1 complex.
  • Demonstrated that IL-10R1 binding induces conformational changes that likely facilitate IL-10R2 engagement.

Conclusions:

  • IL-10R1 binding to IL-10 induces conformational changes that regulate subsequent IL-10R2 binding.
  • The findings provide insights into the structural mechanisms governing the assembly of the ternary IL-10 signaling complex.
  • The elucidated mechanism may be conserved across other class-2 cytokines and their receptors.

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