Related Experiment Videos
Crystal structure of a complex between interferon-gamma and its soluble high-affinity receptor
M R Walter1, W T Windsor, T L Nagabhushan
1Department of Pharmacology, University of Alabama at Birmingham 35294, USA.
Nature
|July 20, 1995
Summary
The crystal structure of interferon-gamma bound to its receptor shows a unique class-2 cytokine complex. This reveals how interferon-gamma interacts with cell surface receptors, impacting immune responses.
Area of Science:
- Structural biology
- Immunology
- Biochemistry
Background:
- Interferon-gamma (IFN-γ) is a crucial cytokine in immune regulation.
- Understanding IFN-γ's interaction with its receptor is key to deciphering its biological functions.
- Previous structural data on cytokine-receptor complexes primarily involved class-1 receptors.
Purpose of the Study:
- To determine the high-resolution crystal structure of the interferon-gamma and its high-affinity receptor complex.
- To provide the first structural insights into a class-2 cytokine-receptor interaction.
Main Methods:
- X-ray crystallography was employed to resolve the complex structure.
- Structural analysis focused on the binding interface and conformational changes.
Main Results:
- The crystal structure reveals a novel 1:2 complex stoichiometry: one IFN-γ homodimer binds two receptor molecules.
- The two receptor molecules do not interact and are spaced apart, differing from class-1 cytokine receptor complexes.
- Receptor binding induces a conformational change in the IFN-γ AB loop, forming a 3(10) helix.
Conclusions:
- This study presents the first structural view of a class-2 cytokine-receptor complex.
- The unique binding mode highlights differences between class-1 and class-2 cytokine receptor interactions.
- The observed conformational change in IFN-γ upon receptor binding may be critical for signal transduction.