1evs: Difference between revisions
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[[Image:1evs.jpg|left|200px]] | [[Image:1evs.jpg|left|200px]] | ||
'''CRYSTAL STRUCTURE OF HUMAN ONCOSTATIN M''' | {{Structure | ||
|PDB= 1evs |SIZE=350|CAPTION= <scene name='initialview01'>1evs</scene>, resolution 2.2Å | |||
|SITE= | |||
|LIGAND= | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''CRYSTAL STRUCTURE OF HUMAN ONCOSTATIN M''' | |||
==Overview== | ==Overview== | ||
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. | 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. | ||
==Disease== | |||
Known disease associated with this structure: Amyloidosis, primary localized cutaneous OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601743 601743]] | |||
==About this Structure== | ==About this Structure== | ||
1EVS is a [ | 1EVS is a [[Single protein]] structure of sequence from [http://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]. | ||
==Reference== | ==Reference== | ||
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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/10997905 10997905] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: gp130 binding cytokine]] | [[Category: gp130 binding cytokine]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:00:56 2008'' | ||
