Interferon: Difference between revisions
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<StructureSection load='2hym' size='350' side='right' caption='Human interferon α/β receptor complex with interferon α-2 (PDB code [[2hym]])' scene=' | <StructureSection load='2hym' size='350' side='right' caption='Human interferon α/β receptor (grey) complex with interferon α-2 (green) (PDB code [[2hym]])' scene=''> | ||
__TOC__ | __TOC__ | ||
==Function== | ==Function== | ||
'''Interferons''' were the first cytokines discovered and were identified by Isaacs and Lindenmann. These proteins were classified as interferons because they interfered with virus growth.<ref name="Isaacs" /> The initial experiments performed poorly characterized the interferons, and was based merely on bioactivity. Advances in scientific instrumentation and technique have allowed for greater understanding and visualization of not only the structure but also the mechanisms of the various types of inteferons.<ref name="Structure">PMID:2413490</ref> The interferons were originally classified as leukocyte ('''interferon-α'''), fibroblast ('''interferon-β'''), and | '''Interferons''' were the first cytokines discovered and were identified by Isaacs and Lindenmann. These proteins were classified as interferons because they interfered with virus growth.<ref name="Isaacs" /> The initial experiments performed poorly characterized the interferons, and was based merely on bioactivity. Advances in scientific instrumentation and technique have allowed for greater understanding and visualization of not only the structure but also the mechanisms of the various types of inteferons.<ref name="Structure">PMID:2413490</ref> The interferons were originally classified as leukocyte ('''interferon-α'''), fibroblast ('''interferon-β'''), and immune ('''interferon-γ'''), although today they are classified into types I (α, β, ε, κ, ω), II (γ), and III (λ).<ref name="Isaacs" /><ref name="Structure" /> | ||
{{Clear}} | {{Clear}} | ||
*'''Interferon-γ''' induces macrophage stimulation toward antimicrobial and antitumor pathways<ref>PMID:14525967</ref> | |||
*'''Interferon-λ''' has dual role in innate immunity and in long-term immunomodulatory effects on T- and B-cells<ref>PMID:28293236</ref> | |||
*'''Interferon-τ''' functions in ensuring pregnancy continuation in ovine and bovine conceptuses<ref>PMID:17662642</ref> | |||
*'''Interferon-ω''' has potent antiviral activity against several DNA and RNA viruses<ref>PMID:9345398</ref> | |||
==Type I== | ==Type I== | ||
Type I interferons are homologous helical cytokines that effect a wide variety of cells pleiotropically. These effects range from antiviral activity to antibacterial, antiprozoal, immunodulatory, and cell growth regulatory functions. Without Type I interferons, the survival of the higher vertebrates would be impossible. Because of their strong antiviral and antiproliferative effects, these interferons are used in the treatment of numerous cancers, hepatitis C, and multiple sclerosis. | Type I interferons are homologous helical cytokines that effect a wide variety of cells pleiotropically. These effects range from antiviral activity to antibacterial, antiprozoal, immunodulatory, and cell growth regulatory functions. Without Type I interferons, the survival of the higher vertebrates would be impossible. Because of their strong antiviral and antiproliferative effects, these interferons are used in the treatment of numerous cancers, hepatitis C, and multiple sclerosis. See [[Multiple sclerosis]]. | ||
All type I interferons bind to a cell surface receptor consisting of two subunits: IFNAR1 and IFNAR2. These receptors belong to a class II helical cytokine receptor family (HCRII). Other members of this family include the interferon-γ receptor (IFNGR), tissue factor (TF), the interleukin 10 receptor (IL20R1 and IL20R2), IL-28BP, IFNLR, and IL28Rα.<ref>PMID:17001036</ref>. | All type I interferons bind to a cell surface receptor consisting of two subunits: IFNAR1 and IFNAR2. These receptors belong to a class II helical cytokine receptor family (HCRII). Other members of this family include the interferon-γ receptor (IFNGR), tissue factor (TF), the interleukin 10 receptor (IL20R1 and IL20R2), IL-28BP, IFNLR, and IL28Rα.<ref>PMID:17001036</ref>. <br /> | ||
See more details in [[IntronA (Interferon alpha 2b)]] | |||
===Interferon-α=== | ===Interferon-α=== | ||
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The low-affinity receptor chain, IFNAR1, also <scene name='User:David_Canner/Workbench3/Morph_4/4'>undergoes major conformational changes</scene> upon ligand binding. When using D1 as anchor, D3 is moving inwards (toward the ligand) by ~15 Å. This would generate an even larger movement of the membrane-proximal SD4 domain and the transmembrane helix. The conformational changes in IFNAR1 are necessary to form the full spectrum of interactions with the IFN ligand, and to form a stable signaling complex that is able to instigate downstream signaling. In contrast to SD3, SD4 seems to be highly flexible (even more than D2 of IFNAR2). One might suggest that the conformational changes in IFNAR1 by itself will be responsible for a reduced binding affinity of IFNAR1 and may slow down the rate of ligand association to IFNAR1 directly from solution. | The low-affinity receptor chain, IFNAR1, also <scene name='User:David_Canner/Workbench3/Morph_4/4'>undergoes major conformational changes</scene> upon ligand binding. When using D1 as anchor, D3 is moving inwards (toward the ligand) by ~15 Å. This would generate an even larger movement of the membrane-proximal SD4 domain and the transmembrane helix. The conformational changes in IFNAR1 are necessary to form the full spectrum of interactions with the IFN ligand, and to form a stable signaling complex that is able to instigate downstream signaling. In contrast to SD3, SD4 seems to be highly flexible (even more than D2 of IFNAR2). One might suggest that the conformational changes in IFNAR1 by itself will be responsible for a reduced binding affinity of IFNAR1 and may slow down the rate of ligand association to IFNAR1 directly from solution. | ||
==See Also== | |||
*[[Interferon receptor|Interferon receptor]] | |||
*[[Interferon regulatory factor]] | |||
*[[Multiple sclerosis|Multiple sclerosis]] | |||
*[[Journal:Cell:1|Structural linkage between ligand discrimination and receptor activation by type I interferons]] | |||
==3D Structures of interferon== | ==3D Structures of interferon== | ||
[[Interferon 3D structures]] | |||
</StructureSection> | |||
==References== | |||
<references /> | |||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||