Sandbox Reserved 777: Difference between revisions
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== Structure == | == Structure == | ||
[[Image:4helixbundle.png|300px|left|thumb|The four-helix bundle. Image built in Pymol using PDB 2H24]] | [[Image:4helixbundle.png|300px|left|thumb|The four-helix bundle. Image built in Pymol using PDB 2H24]] | ||
The cytokine structure is an intercalated dimer of two identical polypeptide chains, each 178 amino acids in length.<ref>Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the Interleukin-10 receptor. Annu. Rev. Immunol. 2001.19:683-765</ref> The monomers are made up of six amphipathic helices, with two helices of one monomer interacting with four of the other monomer, creating two distinct domains.A four-helix bundle is made up of helices A, C, D and F’ (and A’, C’ D’ and F). This feature is a signature element of all helical cytokines. | The cytokine structure is an intercalated dimer of two identical polypeptide chains, each 178 amino acids in length.<ref>Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the Interleukin-10 receptor. Annu. Rev. Immunol. 2001.19:683-765</ref> The monomers are made up of six amphipathic helices, with two helices of one monomer interacting with four of the other monomer, creating two distinct domains.A four-helix bundle is made up of helices A, C, D and F’ (and A’, C’ D’ and F). This feature is a signature element of all helical cytokines.<ref>Zdanov, A. Structural analysis of cytokines comprising the IL-10 family. Cytokine Growth Factor Rev. 2010; 21:325-330</ref> The structure is stabilized by <scene name='56/564053/Il-10_disulfide_bonds/2'>two disulfide bridges</scene> formed between the first and third cysteine residues and the second and fourth cysteine residues (Cys12 with Cys108, and Cys62 with Cys114). In the image, the disulfide bridges are shown in yellow. Reduction of the disulfide bonds in recombinant IL-10 has been shown to reduce helical content measured by circular dichroism and results in a lack of in vitro biological activity.<ref>Windsor WT, Syto R, Tsarbopoulos A, et al. Disulfide bond assignments and secondary structure analysis of human and murine interleukin 10. Biochemistry. 1993; 32:8807-8815</ref>[[Image:1ilk bio r 500.jpg |right|thumb| another view of the biologically active homodimer]] | ||
== Protein Expression == | == Protein Expression == | ||
IL-10 is a broadly expressed cytokine, usually in response to a stimulus. The gene is located on chromosome 1 and encodes a 178 amino acid peptide. It is translated by cells of the adaptive immune system through a variety of T- and B-cells, as well as by the innate immune system through dendritic cells, natural killer cells, mast cells, macrophages, eosinophils and neutrophils. | IL-10 is a broadly expressed cytokine, usually in response to a stimulus. The gene is located on chromosome 1 and encodes a 178 amino acid peptide. It is translated by cells of the adaptive immune system through a variety of T- and B-cells, as well as by the innate immune system through dendritic cells, natural killer cells, mast cells, macrophages, eosinophils and neutrophils.<ref>Saraiva M and O’Garra A. The regulation of IL-10 production by immune cells. Nature Reviews Immunology. 2010 Mar; 10:170-181</ref> The exact signaling pathway that leads to IL-10 expression in most immune cells is unclear; however, it is known that the extra-cellular signal regulated kinase (ERK) cascade is one pathway activated in macrophages and myeloid dendritic cells that does lead to IL-10 expression.<ref>Saraiva M and O’Garra A. The regulation of IL-10 production by immune cells. Nature Reviews Immunology. 2010 Mar; 10:170-181</ref> | ||
== Mechanism of Action == | == Mechanism of Action == | ||
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8) Thompson Reuters. Web. 16Nov2013. <http://pathwaymaps.com/maps/531/> | 8) Thompson Reuters. Web. 16Nov2013. <http://pathwaymaps.com/maps/531/> | ||
