Interferon‐γ binds to heparan sulfate by a cluster of amino acids located in the C‐terminal part of the molecule

  title={Interferon‐$\gamma$ binds to heparan sulfate by a cluster of amino acids located in the C‐terminal part of the molecule},
  author={Hugues Lortat-Jacob and Jean Alexis Grimaud},
  journal={FEBS Letters},

Insights into the mechanism by which interferon-γ basic amino acid clusters mediate protein binding to heparan sulfate.

The binding mechanism described herein, by which the D2 domain kinetically drives the interaction, has important functional consequences and gives a structural framework to better understand how specific are the interactions between proteins and heparin.

Binding of interferon gamma by glycosaminoglycans: a strategy for localization and/or inhibition of its activity.

Analysis of the ability of Glycosaminoglycans to interact with human interferon gamma and the effect of those interactions on its biologic activity suggests important regulatory roles for GAGs on the activity of IFN-gamma in vivo.

Glycosaminoglycans alter the conformation of interferon-gamma.

It is suggested that heparin and chondroitin sulfate modulate IFN-gamma activity by causing structural changes in the IFN -gamma dimer.

NMR characterization of the interaction between the C-terminal domain of interferon-gamma and heparin-derived oligosaccharides.

Evidence is provided of a binding through electrostatic interactions between the charged side chains of the protein and the sulphate groups of heparin that does not induce specific conformation of the C-terminal part of IFNgamma.

Heparin Decreases the Blood Clearance of Interferon-γ and Increases Its Activity by Limiting the Processing of Its Carboxyl-terminal Sequence*

The data demonstrate that the blood clearance of the cytokine is a non-receptor-mediated process and that in vivo the local concentration of heparan sulfate/heparin-like molecules regulates IFN-γ activity by a unique mechanism involving a controlled processing of its carboxyl-terminal sequence.

The Heparan Sulfate Binding Sequence of Interferon-γ Increased the On Rate of the Interferon-γ-Interferon-γ Receptor Complex Formation*

It is found that IFNγ bound to heparin displayed a strongly reduced affinity for its receptor, which is consistent with the fact that a cluster of basic amino acids in the carboxyl-terminal sequence of the cytokine was involved both inheparin and receptor recognition.

Heparin inhibits the antiparasitic and immune modulatory effects of human recombinant interferon‐γ

This study analyzes the effect of heparin and heparan sulfate on three different IFN‐γ‐mediated activities inducible in human glioblastoma cells.



Reduced receptor binding by a human interferon-gamma fragment lacking 11 carboxyl-terminal amino acids.

The results suggest that the carboxyl terminus of human IFN-gamma contributes significantly to the formation of the receptor-binding site of the molecule.

Mutational analysis of the C-terminus of human interferon-gamma.

The results suggest that most residues within the cassette can be altered without significant effects on biological activity, and confirm earlier observations of the important role of basic residues in the 128-131 region of the molecule for biological activity.