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PDBsum entry 1evs
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure and functional dissection of the cytostatic cytokine oncostatin m.
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Authors
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M.C.Deller,
K.R.Hudson,
S.Ikemizu,
J.Bravo,
E.Y.Jones,
J.K.Heath.
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Ref.
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Structure, 2000,
8,
863-874.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 5.
Figure 5. Complimentarity 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. The orientation for
hOSM site 2 is rotated 90° from that in Figure 4 whereas gp130
is rotated by 180° from its orientation relative to hOSM in the
putative interaction complex, as in the opening of a book.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2000,
8,
863-874)
copyright 2000.
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