In 1954, substances that protected cells from viral infection were discovered and named IFN (interferon). This family of cytokines, which were the first to be used in clinical therapy, is classified into type I and II IFNs. Type I mainly consists of IFNα and IFNβ subtypes, which are structurally related and bind to a common receptor. IFNγ, the sole type II IFN, is structurally unrelated, binds to a different receptor and, as a dimer, strongly interacts with HS (heparan sulphate). In addition to its antiviral activity, it modulates nearly all phases of immune and inflammatory responses. IFNγ binding to HS controls the blood clearance, the subsequent tissue targeting and the local accumulation of the cytokine. It also regulates IFNγ activity by a unique mechanism involving a controlled processing of the C-terminal peptide. The binding site encompasses an N-acetylated glucosamine-rich domain separating two highly sulphated sequences that each binds to one IFNγ monomer. Based on this template, a set of glycoconjugate mimetics that would mimic the IFNγ binding site has been synthesized. One of these molecules displays high affinity for the cytokine and inhibits binding to both HS and IFNγR (IFNγ receptor), the cell-surface receptor. These results validate the HS structural determinants for IFNγ recognition, and provide a new strategy to inhibit IFNγ in a number of diseases in which the cytokine has been identified as a target.
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Conference Article|
May 22 2006
Interferon and heparan sulphate
H. Lortat-Jacob
H. Lortat-Jacob
1
1Institut de Biologie Structurale UMR 5075 CEA-CNRS-UJF, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France
1email Hugues.Lortat-Jacob@ibs.fr
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Publisher: Portland Press Ltd
Received:
December 20 2005
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2006 The Biochemical Society
2006
Biochem Soc Trans (2006) 34 (3): 461–464.
Article history
Received:
December 20 2005
Citation
H. Lortat-Jacob; Interferon and heparan sulphate. Biochem Soc Trans 1 June 2006; 34 (3): 461–464. doi: https://doi.org/10.1042/BST0340461
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