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| {{STRUCTURE_1evs| PDB=1evs | SCENE= }} | | {{STRUCTURE_1evs| PDB=1evs | SCENE= }} |
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| '''CRYSTAL STRUCTURE OF HUMAN ONCOSTATIN M'''
| | ===CRYSTAL STRUCTURE OF HUMAN ONCOSTATIN M=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_10997905}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 10997905 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_10997905}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: 4-helix bundle]] | | [[Category: 4-helix bundle]] |
| [[Category: Gp130 binding cytokine]] | | [[Category: Gp130 binding cytokine]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 15:34:37 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 02:05:47 2008'' |
