Interferon-gamma
From Wikipedia, the free encyclopedia
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Interferon gamma
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| Identifiers | |
| Symbol | IFNG |
| HUGO | 5438 |
| Entrez | 3458 |
| OMIM | 147570 |
| RefSeq | NM_000619 |
| UniProt | P01579 |
| PDB | 1FG9 |
| Other data | |
| Locus | Chr. 12 q24.1 |
Interferon-gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons.[1] This interferon was originally called macrophage-activating factor.
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[edit] Structure of IFN-γ
The IFN-γ monomer consists of a core of six α-helices and an extended unfolded sequence in the C-terminal region.[2][3] This is shown in the structural models below. The α-helices in the core of the structure are numbered 1 to 6.
The biologically active dimer is formed by anti-parallel inter-locking of the two monomers as shown below. In the cartoon model, one monomer is shown in red, the other in blue.
The structural models shown above (see protein data bank code 1FG9) are all shortened at their C-termini by 17 amino acids. Full length IFN-γ is 143 amino acids in length, the models are 126 amino acids in length. Affinity for the glycosaminoglycan heparan sulphate resides solely within the deleted sequence of 17 amino acids.[4]
[edit] Biological activity
In contrast to interferon-α and interferon-β which can be expressed by all cells, IFN-γ is secreted by T lymphocytes and NK cells only. Also known as immune interferon, IFN-γ is the only Type II interferon. It is serologically distinct from Type I interferons and it is acid-labile, while the type I variants are acid-stable.
IFN-γ has antiviral, immunoregulatory, and anti-tumour properties.[5] It alters transcription in up to 30 genes producing a variety of physiological and cellular responses. Activation by IFN-γ is achieved by its interaction with a heterodimeric receptor consisting of IFNGR1 & IFNGR2 (interferon gamma receptors). IFN-γ binding to the receptor activates the JAK-STAT pathway. In addition, IFN-γ activates APCs and promotes Th1 differentiation by upregulating the transcription factor T-bet.
IFN-γ is the hallmark cytokine of Th1 cells (Th2 cells produce IL-4). NK cells and CD8+ cytotoxic T cells also produce IFN-γ. IFN-γ suppresses osteoclast formation by rapidly degrading the RANK adaptor protein TRAF6 in the RANK-RANKL signaling pathway, which otherwise stimulates the production of NFκB.
[edit] Therapeutic uses
| Image:Interferon-gamma.png | |
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Interferon-gamma
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| Systematic (IUPAC) name | |
| Human interferon gamma-1b | |
| Identifiers | |
| CAS number | 98059-61-1 |
| ATC code | L03 |
| PubChem | ? |
| DrugBank | |
| Chemical data | |
| Formula | C761H1206N214O225S6 |
| Mol. mass | 17145.6 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status | |
| Routes | ? |
Interferons are used to treat infectious diseases, but can also precipitate autoimmunity (in up to 19% people treated with these cytokines).[citation needed]
[edit] References
- ^ Gray, P. W. and Goeddel, D. V. (1982). "Structure of the human immune interferon gene". Nature 298: 859-863.
- ^ Ealick, S. E., Cook, W. J. et al. (1991). "Three-dimensional structure of recombinant human interferon-gamma". Science 252: 698-702.
- ^ Thiel, D. J. et al. (2000). "Observation of an unexpected third receptor molecule in the crystal structure of human interferon-γ receptor complex". Structure 8 (9): 927-936.
- ^ Vanhaverbeke, C. Simorre, J-P. et al. (2004). "NMR characterization of the interaction between the C-terminal domain of interferon-γ and heparin-derived oligosaccharides" 384: 93-99.
- ^ Schroder et al. (2004). "Interferon-γ an overview of signals, mechanisms and functions". Journal of Leukocyte Biology 75: 163-189.
