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A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to

A Zdanov1, C Schalk-Hihi, A Gustchina

  • 1Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA.

Structure (London, England : 1993)
|June 15, 1995
PubMed

Insights

The crystal structure of Interleukin (IL)-10 reveals a tight V-shaped dimer, offering insights into its biological activity and receptor interactions. This finding is crucial for understanding cytokine function and developing new therapeutics.

Area of Science:

  • Structural Biology
  • Immunology
  • Protein Crystallography

Background:

  • Interleukin (IL)-10 is a cytokine that suppresses the production of other regulatory factors like interferon gamma (IFN-gamma) and IL-2.
  • The dimeric form of IL-10 in solution is thought to be involved in receptor binding, but its precise nature remained uncharacterized.
  • Understanding the atomic structure of IL-10 is essential for interpreting its biological functions and designing targeted therapeutic agents.

Purpose of the Study:

  • To determine the atomic structure of recombinant human IL-10.
  • To elucidate the structural basis of IL-10 dimerization.
  • To provide a foundation for understanding IL-10's biological activity and receptor interactions.

Main Methods:

  • X-ray crystallography was employed to solve the structure of recombinant human IL-10.
  • High-resolution data collection (1.8 Å) and crystallographic refinement were performed.
  • Structural analysis focused on the dimeric interface and helical bundle organization.

Main Results:

  • The X-ray crystal structure of human IL-10 was determined at 1.8 Å resolution.
  • IL-10 forms a tight dimer with a V-shaped conformation, comprising two interpenetrating subunits.
  • The structure features a bundle of six alpha-helices, with four from one subunit and two from the other, resembling other helical cytokines but with unique topological features.

Conclusions:

  • The determined structure of IL-10 reveals a topological similarity to IFN-gamma, suggesting a potential link between their biological effects.
  • The atomic model provides insights into potential mechanisms of dimer-to-monomer conversion and identifies putative receptor interaction sites.
  • The high-resolution structure demonstrates that internal disorder is not a universal characteristic of helical cytokines.
Abstract

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