Interferon

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[[Image:InterferonSignalingPathway.png|525px|right|thumb|Interferon Pathway<ref name="Isaacs">[http://www.jbc.org/content/282/28/20045.full?sid=cbf08059-44d4-4957-8ea7-0351cab9c2ac] Samuel, C.E. "Interferons, Interferon Receptors, Signal Transducer and Transcriptional Activators, and Inteferon Regulatory Factors." ''J Biol Chem'' 2007 282: 20045-20046. First Published on May 14, 2007, doi:10.1074/jbc.R700025200</ref>]]
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[[Image:InterferonSignalingPathway.png|600px|right|thumb|Interferon Pathway<ref name="Isaacs">[http://www.jbc.org/content/282/28/20045.full?sid=cbf08059-44d4-4957-8ea7-0351cab9c2ac] Samuel, C.E. "Interferons, Interferon Receptors, Signal Transducer and Transcriptional Activators, and Inteferon Regulatory Factors." ''J Biol Chem'' 2007 282: 20045-20046. First Published on May 14, 2007, doi:10.1074/jbc.R700025200</ref>]]
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'''Interferons''' were the first cytokines discovered and were identified by Isaacs and Lindenmann. These proteins were identified 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>
'''Interferons''' were the first cytokines discovered and were identified by Isaacs and Lindenmann. These proteins were identified 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>
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Interferons -α and -β interact with a receptor at the cell surface.<ref>[http://www.jbc.org/content/282/28/20045.full?sid=cbf08059-44d4-4957-8ea7-0351cab9c2ac] Samuel, C.E. "Interferons, Interferon Receptors, Signal Transducer and Transcriptional Activators, and Inteferon Regulatory Factors." ''J Biol Chem'' 2007 282: 20045-20046. First Published on May 14, 2007, doi:10.1074/jbc.R700025200</ref> This receptor has <scene name='Multiple_sclerosis/Ifnr_domains_labeled/1'>three domains</scene>: an
Interferons -α and -β interact with a receptor at the cell surface.<ref>[http://www.jbc.org/content/282/28/20045.full?sid=cbf08059-44d4-4957-8ea7-0351cab9c2ac] Samuel, C.E. "Interferons, Interferon Receptors, Signal Transducer and Transcriptional Activators, and Inteferon Regulatory Factors." ''J Biol Chem'' 2007 282: 20045-20046. First Published on May 14, 2007, doi:10.1074/jbc.R700025200</ref> This receptor has <scene name='Multiple_sclerosis/Ifnr_domains_labeled/1'>three domains</scene>: an
<scene name='Multiple_sclerosis/Ifnr_n_domain_labeled/1'>N-domain</scene>, with two disulfide bonds, a <scene name='Multiple_sclerosis/Ifnr_c_domain_labeled/1'>C-domain</scene>, with one disulfide bond, and a <scene name='Multiple_sclerosis/Ifnr_linker_region_labeled/1'>linker region</scene>. The <scene name='Multiple_sclerosis/Ifnr_termini_labeled/1'>termini regions</scene> of the receptor have no secondary structure, allowing for some serious flexibility, leading to <scene name='Multiple_sclerosis/Ifnr_clash_n-c/1'>eight clashes amongst the domains</scene>.<ref name="Interferon Receptor Structure">PMID:12842042</ref>
<scene name='Multiple_sclerosis/Ifnr_n_domain_labeled/1'>N-domain</scene>, with two disulfide bonds, a <scene name='Multiple_sclerosis/Ifnr_c_domain_labeled/1'>C-domain</scene>, with one disulfide bond, and a <scene name='Multiple_sclerosis/Ifnr_linker_region_labeled/1'>linker region</scene>. The <scene name='Multiple_sclerosis/Ifnr_termini_labeled/1'>termini regions</scene> of the receptor have no secondary structure, allowing for some serious flexibility, leading to <scene name='Multiple_sclerosis/Ifnr_clash_n-c/1'>eight clashes amongst the domains</scene>.<ref name="Interferon Receptor Structure">PMID:12842042</ref>
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===Interferon-ε===
 
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===Interferon-κ===
 
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===Interferon-ω===
 
==Type II==
==Type II==
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__NOTOC__
__NOTOC__
</StructureSection>
</StructureSection>
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=== A comparative representation of three interferons ===
 
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<center>
 
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{|
 
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|<applet load='1ITF.pdb' name='A' size='300' frame='true' align='right' caption='Interferon Alpha' align='left' scene='Interferons/Ifn_alpha/4'/>
 
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|<applet load='1IFA.pdb' name='B' size='300' frame='true' align='right' caption='Interferon Beta' align='left' scene='Interferons/Interferon_beta/3'/>
 
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|<applet load='1HIG.pdb' name='Z' size='300' frame='true' align='right' caption='Interferon Gamma' align='left' scene='Interferons/Ifn_gamma/4'/>
 
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|}
 
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{{Clear}}
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==References==
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<references />
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==Relevant 3D Structures==
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===Interferon-α===
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[[rh2]], [[1itf]] - ''Homo sapiens''
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===Interferon-β===
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[[1au1]] - ''Homo sapiens''
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[[1ifa]], [[1wu3]] - ''Mus musculus''
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===Inteferon-α/β Receptors===
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[[3s8w]], [[3s98]]
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===Interferon-α/β Receptors in Complex with Interferon-α===
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'''Synchronize the three applets showing interferons alpha, beta, and gamma by clicking the checkbox'''
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[[3oq3]], [[3se3]], [[3se4]], [[1n6u]], [[1n6v]], [[2hym]], [[2kz1]], [[2lag]], [[3s9d]] - ''Homo sapiens''
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<jmol>
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<jmolCheckbox>
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jmolSetTarget('Z')
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jmolScript('sync jmolAppletA,jmolAppletB;sync on;sync * "set syncscript false;set syncmouse true;select *;translateSelected @{-{visible}.xyz};center visible;zoom 0" ')
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<scriptWhenChecked> sync jmolAppletB,jmolAppletZ </scriptWhenChecked>
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<scriptWhenUnchecked> sync OFF</scriptWhenUnchecked>
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<text> Synchronize</text>
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</jmolCheckbox>
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</jmol>
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</center>
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Revision as of 00:32, 24 April 2012

Interferon Pathway
Interferon Pathway[1]

Interferons were the first cytokines discovered and were identified by Isaacs and Lindenmann. These proteins were identified as interferons because they interfered with virus growth.[1] 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.[2]

The interferons were originally classified as leukocyte (interferon-α), fibroblast (interferon-β), and immmune (interferon-γ), although today they are classified into types I (α and β) and II (γ). This classification serves to give a better understanding of the similarities between α and β that does not exist between these type I interferons and interferon-γ.[2] In addition to interferons-α and -β, type I interferons also encompass three other differentiable proteins: interferon-ε, interferon-κ, and interferon-ω.

Click on the green links to the left to view the structural aspects of interferons. PDB ID: 2hym)

Drag the structure with the mouse to rotate


Contents

References

  1. ↑ 1.0 1.1 [1] Samuel, C.E. "Interferons, Interferon Receptors, Signal Transducer and Transcriptional Activators, and Inteferon Regulatory Factors." J Biol Chem 2007 282: 20045-20046. First Published on May 14, 2007, doi:10.1074/jbc.R700025200
  2. ↑ 2.0 2.1 Langer JA, Pestka S. Structure of interferons. Pharmacol Ther. 1985;27(3):371-401. PMID:2413490
  3. ↑ Quadt-Akabayov SR, Chill JH, Levy R, Kessler N, Anglister J. Determination of the human type I interferon receptor binding site on human interferon-alpha2 by cross saturation and an NMR-based model of the complex. Protein Sci. 2006 Nov;15(11):2656-68. Epub 2006 Sep 25. PMID:17001036 doi:10.1110/ps.062283006
  4. ↑ Quadt-Akabayov SR, Chill JH, Levy R, Kessler N, Anglister J. Determination of the human type I interferon receptor binding site on human interferon-alpha2 by cross saturation and an NMR-based model of the complex. Protein Sci. 2006 Nov;15(11):2656-68. Epub 2006 Sep 25. PMID:17001036 doi:10.1110/ps.062283006
  5. ↑ Voet, D., Voet, J.G., and C. Pratt. Fundamentals of Biochemistry 3rd Edition. Hoboken, NJ: John Wiley and Sons, 2008. Print.
  6. ↑ Kudo M. Management of hepatocellular carcinoma: from prevention to molecular targeted therapy. Oncology. 2010 Jul;78 Suppl 1:1-6. Epub 2010 Jul 8. PMID:20616576 doi:10.1159/000315222
  7. ↑ http://www.uniprot.org/uniprot/P00784
  8. ↑ [2] Samuel, C.E. "Interferons, Interferon Receptors, Signal Transducer and Transcriptional Activators, and Inteferon Regulatory Factors." J Biol Chem 2007 282: 20045-20046. First Published on May 14, 2007, doi:10.1074/jbc.R700025200
  9. ↑ Chill JH, Quadt SR, Levy R, Schreiber G, Anglister J. The human type I interferon receptor: NMR structure reveals the molecular basis of ligand binding. Structure. 2003 Jul;11(7):791-802. PMID:12842042

Relevant 3D Structures

Interferon-α

rh2, 1itf - Homo sapiens

Interferon-β

1au1 - Homo sapiens

1ifa, 1wu3 - Mus musculus

Inteferon-α/β Receptors

3s8w, 3s98


Interferon-α/β Receptors in Complex with Interferon-α

3oq3, 3se3, 3se4, 1n6u, 1n6v, 2hym, 2kz1, 2lag, 3s9d - Homo sapiens

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