The solution structure of the membrane-proximal cytokine receptor domain of the human interleukin-6 receptor

Related Experiment Video

Updated: Jul 20, 2026

Identification of Functional Protein Regions Through Chimeric Protein Construction
11:39

Identification of Functional Protein Regions Through Chimeric Protein Construction

Published on: January 8, 2019

Oliver Hecht1, Andrew J Dingley, Andreas Schwanter

  • 1Biochemisches Institut der Christian-Albrechts-Universität Kiel, Olshausenstr. 40, D-24118 Kiel, Germany.

Biological Chemistry
|September 16, 2006
PubMed

Insights

Researchers determined the structure of the IL-6 receptor's third fibronectin-like domain (IL-6R-D3). This domain is crucial for interleukin-6 (IL-6) binding, providing over 90% of the binding energy.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Immunology

Background:

  • Interleukin-6 (IL-6) and its related cytokines utilize receptors with modular structures comprising immunoglobulin-like and fibronectin type III-like domains.
  • These receptors feature a conserved cytokine receptor homology region with specific cysteine and amino acid motifs.
  • IL-6 binding involves an initial interaction with its alpha-receptor, followed by engagement with the gp130 signal transducer.

Purpose of the Study:

  • To elucidate the three-dimensional structure of the IL-6 receptor's third fibronectin-like domain (IL-6R-D3).
  • To understand the structural basis for the high binding affinity of IL-6R-D3 to interleukin-6.

Main Methods:

  • Multidimensional heteronuclear nuclear magnetic resonance (NMR) spectroscopy was employed.
  • Solution structure determination of the IL-6R-D3 domain.

Main Results:

  • The solution structure of the IL-6R-D3 domain was successfully solved.
  • This domain contributes significantly, over 90%, to the binding energy between IL-6 and its receptor.

Conclusions:

  • The IL-6R-D3 domain is the primary determinant of binding affinity for interleukin-6.
  • Understanding the structure of IL-6R-D3 provides insights into cytokine-receptor interactions and potential therapeutic targets.

More Related Videos

Production of Disulfide-stabilized Transmembrane Peptide Complexes for Structural Studies12:05

Production of Disulfide-stabilized Transmembrane Peptide Complexes for Structural Studies

Published on: March 6, 2013

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α11:27

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

Published on: November 2, 2018

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Antibody Structure01:10

Antibody Structure

Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibody Structure01:10

Antibody Structure

Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Multi-pass Transmembrane Proteins and β-barrels01:09

Multi-pass Transmembrane Proteins and β-barrels

In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include: