Multiple sclerosis: Difference between revisions

===Interferon-α, Interferon-β, and Interferon Receptors 1 & 2 ===

Since a PDB reference does not exist for interferon-β interacting with interferon receptors 1 or 2, and a multitude of files exist on <scene name='Multiple_sclerosis/Ifna/1'>interferon-α</scene> interacting with the receptor, a comparison to interferon-α will be made prior to demonstrating the types of bonding that occur between the interferon and its receptor. To see more information regarding interferons, please visit the [[Interferons]] site.

Interferon-α has a 31% sequence homology to interferon-β. It, too, has many <scene name='Multiple_sclerosis/Ifna_labeled/1'>identifiable regions</scene> with two <scene name='Multiple_sclerosis/Ifna_disulfide_bonds/1'>disulfide bonds</scene>: one between the <scene name='Multiple_sclerosis/Ifna_disulfide_bondsn-e/1'>N-terminus and Helix E</scene>, and the other between <scene name='Multiple_sclerosis/Ifna_disulfide_bonds_ab-g/1'>Loop AB and Helix G</scene>. It has seven <scene name='Multiple_sclerosis/Ifna_alphahelices/1'>alpha helices</scene>, as compared to the five of interferon-β, and therefore has several more <scene name='Multiple_sclerosis/Ifna_loops_regions/1'>loop regions.</scene> The helices A, C, and F run <scene name='Multiple_sclerosis/Ifna_parallelacf/2'>parallel</scene> to one another, and <scene name='Multiple_sclerosis/Ifna_antiparallel/1'>anti-parallel</scene> to B, E, and G which run <scene name='Multiple_sclerosis/Ifna_parallel_beg/2'>parallel</scene> to each other.<scene name='Multiple_sclerosis/Ifna_notparalleltoanyoned/1'>Helix D</scene> 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.   

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>, which are all illustrated on the N-terminus region.<ref name="Interferon Receptor Structure">PMID:12842042</ref>

Interferon-α <scene name='Multiple_sclerosis/Ifnawithreceptorcolored/1'>binds</scene> to an interferon receptor mainly with helices C and G. There are many <scene name='Multiple_sclerosis/Ifnawithreceptorintrxns/2'>residues</scene>, shown in ball-and-stick, within 4 angstroms of one another. These residues could form many <scene name='Multiple_sclerosis/Ifnawithreceptorintrxns/5'>different types of bonds</scene>, 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.<ref name="Interferon Receptor Interferon Alpha">PMID:17001036</ref>