Interferon

From Proteopedia

(Difference between revisions)

Revision as of 23:59, 23 April 2012

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

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.

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.^[3]

Interferon-α

Interferon alpha has a 31% sequence homology to interferon beta. It, too, has many with two : one between the , and the other between . It has seven , as compared to the five of interferon-β, and therefore has several more The helices A, C, and F run to one another, and to B, E, and G which run to each other. does not run parallel or anti-parallel to either set, but rather runs at a 45-90 degree angle to them. Helix A consists of residues 10-12; Helix B of 40-43; Helix C of 53-68; Helix D of 70-75; Helix E of 78-100; Helix F of 109-132; and Helix G of 137-158.

Interferon-α to an interferon receptor mainly with helices C and G. There are many within 4 angstroms of one another. These residues could form many , illustrated in white dotted lines. Given that interferon-α does not undergo many structural changes upon binding to interferon receptor II, Quadt-Akabayov et al. have concluded that the binding mechanism is similar to that of a lock and key. While interferon-α and -β bind to the same receptors as one another, the affinities with which they bind to IFNAR1 and IFNAR2 differ. While the binding to IFNAR2 is stronger for both in comparison to IFNAR1, interferon-β has a much stronger affinity for IFNAR1 than interferon-α.^[4]

Interferon-β

is a protein growth factor that stimulates an antiviral defense. Its encoding gene is one of only two known vertebrate structural genes that lacks introns.^[5]

Interferon-β is a relatively simple biological response modifier, with several . It consists of five , as well as multiple interconnecting . Helices A, B and D run , and helices C and E run to the other three helices, but to one another. Helix A consists of residues 6-23; Helix B consists of residues 49-65; Helix C consists of residues 77-91; Helix D consists of residues 112-131; and Helix E consists of residues 135-155.^[6]^[7]

Interferons -α and -β interact with a receptor at the cell surface.^[8] This receptor has : an

, with two disulfide bonds, a , with one disulfide bond, and a . The of the receptor have no secondary structure, allowing for some serious flexibility, leading to .^[9]

Interferon-ε

Interferon-κ

Interferon-ω

Type II

Interferon-γ

A comparative representation of three interferons

Synchronize the three applets showing interferons alpha, beta, and gamma by clicking the checkbox

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Kirsten Eldredge, Alexander Berchansky, Joel L. Sussman, Karl Oberholser, Jaime Prilusky

Retrieved from "http://52.214.119.220/wiki/index.php/Interferon"

@@ Line 1: / Line 1: @@
-[[Image:InterferonSignalingPathway.png|525px|right|thumb|Interferon Pathway<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>]]
+[[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>]]
+'''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>
+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.<ref name="Structure" /> In addition to interferons-α and -β, type I interferons also encompass three other differentiable proteins: interferon-ε, interferon-κ, and interferon-ω.
 {{Clear}}