Sandbox Reserved 830: Difference between revisions
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{{STRUCTURE_1evs| PDB=1evs | SCENE= }} | {{STRUCTURE_1evs| PDB=1evs | SCENE= }} | ||
=== | ===Human Oncostatin M=== | ||
==Introduction== | ==Introduction== | ||
Oncostatin M is encoded by the OSM gene and it is mostly produced in the end of the activation of macrophages and T cells. OSM belongs to the family of gp130 cytokines implying that it signals through the receptors containing gp130. OSM has been shown to have a lot of pleiotropic functions in cell proliferation, differentiation and inflammatory response. Thus, studies highlight its roles in cancer, bone and liver metabolism alteration, as well as in severe inflammatory disease, such as lung and skin inflammatory disease, atherosclerosis, cardiovascular diseases, and rheumatoid polyarthritis. | Oncostatin M is encoded by the OSM gene and it is mostly produced in the end of the activation of macrophages and T cells. OSM belongs to the family of gp130 cytokines implying that it signals through the receptors containing gp130. OSM has been shown to have a lot of pleiotropic functions in cell proliferation, differentiation and inflammatory response. Thus, studies highlight its roles in cancer, bone and liver metabolism alteration, as well as in severe inflammatory disease, such as lung and skin inflammatory disease, atherosclerosis, cardiovascular diseases, and rheumatoid polyarthritis. | ||
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OSM is a compact molecule with dimensions of approximately 20 Å x 27 Å x 56 Å, that fit with the up-up-down-down four-helix bundle structure. | OSM is a compact molecule with dimensions of approximately 20 Å x 27 Å x 56 Å, that fit with the up-up-down-down four-helix bundle structure. | ||
[[Image:Oncostatin structure.png|frame|left|Ribbon colored diagram of hOSM from N-terminus in blue to the C-terminus in red. The two disulphide bonds are shown as ball-and-sticks models with the sulphur atoms represented as yellow spheres. The CD loop as observed in LIF is represented by the transparent dotted section.]] | [[Image:Oncostatin structure.png|frame|left|Ribbon colored diagram of hOSM from N-terminus in blue to the C-terminus in red. The two disulphide bonds are shown as ball-and-sticks models with the sulphur atoms represented as yellow spheres. The CD loop as observed in LIF is represented by the transparent dotted section.]] | ||
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Site 3 of OSM binds to LIFR or OSMR thanks to two residues: Phe160 and Lys163, located in the N-terminal end of helix D. These amino acids are conserved in all cytokines. | Site 3 of OSM binds to LIFR or OSMR thanks to two residues: Phe160 and Lys163, located in the N-terminal end of helix D. These amino acids are conserved in all cytokines. | ||
[[Image:Osm interact osmr.png|frame|left| | [[Image:Osm interact osmr.png|frame|left|Complementarity between the interaction surfaces of hOSM and gp130.The solvent-accessible surfaces of site 2 on hOSM (left) and the cognate binding site on gp130 (right) are displayed with areas contributed by residues implicated in binding highlighted as coloured patches.]] [[Image:Oncostatin site3.jpg|frame|center| Site 3 onfiguration with residues for OSMR and LIFR binding in red.]] | ||
==Functions== | ==Functions== | ||
Oncosatin M binds to two different receptors which are heterodimers: gp130/LIFRα and OSMRβ/gp130. These receptors are present on a lot of different cell lines. | Oncosatin M binds to two different receptors which are heterodimers: gp130/LIFRα and OSMRβ/gp130. These receptors are present on a lot of different cell lines. | ||