Interferon structure

Streuli, M., S. Nagata, and C. Weissman, At least three human type a interferons structure of o2. Science, 1980. 209 1343-49. 

Hemming OJ, Lutfalla G, Levraud JP, Hartmann R. Crystal structure of zebiafish interferons I and II reveals conservation of type I interferon structure in vtatebiates. J Virol. 2011 85 8181-7. 

Cellular cytokines (interferons, G-CSF) and immune response modifiers originally produced from human cells, most often leukocytes, have now been replaced with recombinant products with well-defined structure/function. Futuristic advances in experimental hematology portend development of human blood cells produced from the hemopoetic stem cells. Yet for the foreseeable future, homologous blood donated by healthy, altruistic voluntary blood donors remains the principal source of safe and adequate supply of blood and blood products for transfusion therapy. 

Cytokine receptors are a group of structurally related receptors, which couple to the JAK-STAT pathway. Cytokine receptors function as homodimers or heterooligomers. They are divided into two main subclasses, class I, which contains receptors for a variety of hematopoietic growth factors and interleukins and class II, which contains receptors for interferons and interleukins 10, 20/24 and 22. 

Ajami K, Pitman MR, Wilson CH et al (2008) Stromal cell-derived factors lalpha and Ibeta, inflammatory protein-10 and interferon-inducible T cell chemo-attractant are novel substrates of dipeptidyl peptidase 8. FEBS Lett 582 819-825 Albright AV, Shieh JT, O Connor Ml et al (2000) Characterization of cultured microglia that can be infected by HIV-1. J Neurovirol 6(Suppl 1) S53-S60 Allen SJ, Crown SE, Handel TM (2007) Chemokine receptor structure, interactions, and antagonism. Annu Rev Immunol 25 787-820... 

Wang, Y.-S., Youngster, S., Grace, M., Bausch, J., Bordens, R., and Wyss, D.F. 2002. Structural and biological characterization of pegylated recombinant interferon alpha-2b and its therapeutic implications. Advanced... 

The basic structure of carboxyethylgermanium sesquioxide, a low-toxicity y-interferon inducing agent, consists of a 12-membered ring containing six Ge tetrahedra bridged by oxygen atoms. 

However, only the extracellular domains immediately adjacent to the cell membrane and the (32 microglobulin peptide have clear homology with the immunoglobulin domains. The al and ct2 segments of class I and the al and (31 domains in class II have quite an unusual structure. Class I molecules are present on virtually every cell in the body, the most notable exception being the syncytial trophoblast of the placenta. Class II expression is far more restricted B cells, dendritic cells which present antigen to T cells, and macrophage express abundant class II molecule on their surfaces. However, most other tissues can be induced to express class II molecules under the influence of soluble mediators such as 7-interferon. 

Interferons There are two types of interferons Type I, which includes IFN-a and IFN-jS, and Type II consisting of IFN-y. IFN-a and IFN- 8 have about 30% homology in amino acid sequence. There are two more recently discovered Type I interferons they are called IFN-o and IFN-t. IFN-a and IFN- 8 each have 166 amino acids, and IFN-yhas 143. Both IFN-a and IFN-jS are of single chain structure and bind to the same type of cell surface receptors, whereas IFN-y is a dimer of two identical chains and interacts with another type of receptor. All our cells can produce Type I interferons when infected by viruses, bacteria, and fungi. However, only T cells and natural killer cells can produce... 

Note that the protein kinase, which phosphorylates the IF-GDP complex is structurally similar to the protein kinase that is activated by double-stranded RNA, i.e. the genome of some viruses. This protein kinase phosphorylates the IF-GDP complex in an infected host cell, so that viral peptide synthesis is inhibited and the virus cannot multiply. Synthesis of this kinase is stimulated by the cytokine, interferon, which is released by virus-infected cells as an early-warning system to adjacent cells not yet infected (Chapter 17 see Figure 17.32). 

Roisman LC, Piehler J, Trosset JY et al (2001) Structure of the interferon-receptor complex determined by distance constraints from double-mutant cycles and flexible docking. Proc Natl Acad Sci U S A 98 13231-13236... 

Wang, Y. et al. (2002). Structural and biological characterization of PEGylated recombinant interferon-a2B and its therapeutic implications. Adv. Drug Delivery Rev. 54(4), 547-570. 

Misaki IL, Nagaya H., Fujiyama K., Yanagihara I., Honda T. and Seki T. (2003) N-Hnked glycan structures of mouse interferon-p produced by Bombyx mori larvae. Biochem. Biophys. Res. Commun. 311,979-986. 

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