Crystal structure and functional dissection of the cytostatic cytokine oncostatin M.

Deller, M; Hudson, K; Ikemizu, S; Bravo, J; Jones, E; Heath, J

Journal article

Crystal structure and functional dissection of the cytostatic cytokine oncostatin M.

Abstract:: 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.

Publication status:: Published

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APA Style

Deller, M., Hudson, K., Ikemizu, S., Bravo, J., Jones, E., & Heath, J. (2000). Crystal structure and functional dissection of the cytostatic cytokine oncostatin M. Structure (London, England : 1993), 8(8), 863–874.

MLA Style

Deller, M., et al. “Crystal Structure and Functional Dissection of the Cytostatic Cytokine Oncostatin M.” Structure (London, England : 1993), vol. 8, no. 8, 2000, pp. 863–74.

Chicago Style

Deller, M, K Hudson, S Ikemizu, J Bravo, E Jones, and J Heath. 2000. “Crystal Structure and Functional Dissection of the Cytostatic Cytokine Oncostatin M.” Structure (London, England : 1993) 8 (8): 863–74.
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