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| | <StructureSection load='1evs' size='340' side='right'caption='[[1evs]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='1evs' size='340' side='right'caption='[[1evs]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1evs]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EVS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EVS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1evs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EVS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EVS FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1evs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1evs OCA], [http://pdbe.org/1evs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1evs RCSB], [http://www.ebi.ac.uk/pdbsum/1evs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1evs ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1evs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1evs OCA], [https://pdbe.org/1evs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1evs RCSB], [https://www.ebi.ac.uk/pdbsum/1evs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1evs ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ONCM_HUMAN ONCM_HUMAN]] Growth regulator. Inhibits the proliferation of a number of tumor cell lines. Stimulates proliferation of AIDS-KS cells. It regulates cytokine production, including IL-6, G-CSF and GM-CSF from endothelial cells. Uses both type I OSM receptor (heterodimers composed of LIPR and IL6ST) and type II OSM receptor (heterodimers composed of OSMR and IL6ST). Involved in the maturation of fetal hepatocytes, thereby promoting liver development and regeneration (By similarity).<ref>PMID:1542792</ref> <ref>PMID:1542793</ref> | + | [https://www.uniprot.org/uniprot/ONCM_HUMAN ONCM_HUMAN] Growth regulator. Inhibits the proliferation of a number of tumor cell lines. Stimulates proliferation of AIDS-KS cells. It regulates cytokine production, including IL-6, G-CSF and GM-CSF from endothelial cells. Uses both type I OSM receptor (heterodimers composed of LIPR and IL6ST) and type II OSM receptor (heterodimers composed of OSMR and IL6ST). Involved in the maturation of fetal hepatocytes, thereby promoting liver development and regeneration (By similarity).<ref>PMID:1542792</ref> <ref>PMID:1542793</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bravo, J]] | + | [[Category: Bravo J]] |
| - | [[Category: Deller, M C]] | + | [[Category: Deller MC]] |
| - | [[Category: Heath, J K]] | + | [[Category: Heath JK]] |
| - | [[Category: Hudson, K R]] | + | [[Category: Hudson KR]] |
| - | [[Category: Ikemizu, S]] | + | [[Category: Ikemizu S]] |
| - | [[Category: Jones, E Y]] | + | [[Category: Jones EY]] |
| - | [[Category: 4-helix bundle]]
| + | |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Gp130 binding cytokine]]
| + | |
| Structural highlights
Function
ONCM_HUMAN Growth regulator. Inhibits the proliferation of a number of tumor cell lines. Stimulates proliferation of AIDS-KS cells. It regulates cytokine production, including IL-6, G-CSF and GM-CSF from endothelial cells. Uses both type I OSM receptor (heterodimers composed of LIPR and IL6ST) and type II OSM receptor (heterodimers composed of OSMR and IL6ST). Involved in the maturation of fetal hepatocytes, thereby promoting liver development and regeneration (By similarity).[1] [2]
Publication Abstract from PubMed
BACKGROUND: The cytokine oncostatin M (OSM) inhibits growth of certain tumour-derived cells, induces proliferation in other cell types (e.g. haemangioblasts) and is a mediator of inflammatory responses. Its mechanism of action is via specific binding to gp130 and either the leukaemia inhibitory factor receptor (LIFR) or oncostatin M receptor (OSMR) systems at the cell surface to form an active signalling complex. RESULTS: We report here the crystal structure of human oncostatin M (hOSM) along with mutagenesis data which map the receptor-binding epitopes of the molecule. The structure was determined to a resolution of 2.2 A and conforms to the haematopoietin cytokine up-up-down-down four-helix bundle topology. The site 2 epitope, responsible for gp130 binding, is centred around Gly120 which forms a 'dimple' on the surface of the molecule located on helices A and C. The site 3 motif, responsible for LIFR and OSMR binding, consists of a protruding Phe160/Lys163 pair located at the start of helix D. CONCLUSIONS: The data presented allow functional dissection of the receptor-binding interfaces to atomic resolution. Modelling suggests that the gp130 residue Phe169 packs into the site 2 dimple in an analogous fashion to structurally equivalent residues at the growth hormone-growth hormone receptor interface, implying that certain key features may underlie recognition across the whole cytokine/receptor superfamily. Conversely, detailed comparison of the available structures suggests that variations on a common theme dictate the specificity of receptor-ligand interactions within the gp130 family of cytokines.
Crystal structure and functional dissection of the cytostatic cytokine oncostatin M.,Deller MC, Hudson KR, Ikemizu S, Bravo J, Jones EY, Heath JK Structure. 2000 Aug 15;8(8):863-74. PMID:10997905[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nair BC, DeVico AL, Nakamura S, Copeland TD, Chen Y, Patel A, O'Neil T, Oroszlan S, Gallo RC, Sarngadharan MG. Identification of a major growth factor for AIDS-Kaposi's sarcoma cells as oncostatin M. Science. 1992 Mar 13;255(5050):1430-2. PMID:1542792
- ↑ Miles SA, Martinez-Maza O, Rezai A, Magpantay L, Kishimoto T, Nakamura S, Radka SF, Linsley PS. Oncostatin M as a potent mitogen for AIDS-Kaposi's sarcoma-derived cells. Science. 1992 Mar 13;255(5050):1432-4. PMID:1542793
- ↑ Deller MC, Hudson KR, Ikemizu S, Bravo J, Jones EY, Heath JK. Crystal structure and functional dissection of the cytostatic cytokine oncostatin M. Structure. 2000 Aug 15;8(8):863-74. PMID:10997905
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