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PDBsum entry 1jpy
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Immune system
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PDB id
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1jpy
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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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Il-17s adopt a cystine knot fold: structure and activity of a novel cytokine, Il-17f, And implications for receptor binding.
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Authors
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S.G.Hymowitz,
E.H.Filvaroff,
J.P.Yin,
J.Lee,
L.Cai,
P.Risser,
M.Maruoka,
W.Mao,
J.Foster,
R.F.Kelley,
G.Pan,
A.L.Gurney,
A.M.De vos,
M.A.Starovasnik.
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Ref.
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EMBO J, 2001,
20,
5332-5341.
[DOI no: ]
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PubMed id
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Abstract
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The proinflammatory cytokine interleukin 17 (IL-17) is the founding member of a
family of secreted proteins that elicit potent cellular responses. We report a
novel human IL-17 homolog, IL-17F, and show that it is expressed by activated T
cells, can stimulate production of other cytokines such as IL-6, IL-8 and
granulocyte colony-stimulating factor, and can regulate cartilage matrix
turnover. Unexpectedly, the crystal structure of IL-17F reveals that IL-17
family members adopt a monomer fold typical of cystine knot growth factors,
despite lacking the disulfide responsible for defining the canonical
"knot" structure. IL-17F dimerizes in a parallel manner like
neurotrophins, and features an unusually large cavity on its surface.
Remarkably, this cavity is located in precisely the same position where nerve
growth factor binds its high affinity receptor, TrkA, suggesting further
parallels between IL-17s and neurotrophins with respect to receptor recognition.
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Figure 4.
Figure 4 The structure of IL-17F. (A) Ribbon trace of the IL-17F
monomer. Strands are labeled. Disulfides are shown as
ball-and-stick representation with the sulfur atoms colored
yellow. Glycosylation of Asn53 is indicated by a purple ball.
Inset shows a cartoon representation of the canonical cystine
knot fold. Cysteine residues are indicated by filled circles;
those present in IL-17 proteins are yellow, whereas the two that
are missing are black. (B) Ribbon trace of the IL-17F dimer.
Disulfides are shown as in (A). (C) The structure of NGF from
the NGF -TrkA complex (Wiesmann et al., 1999; Protein Data Bank
code 1WWW); a disordered loop connects strands 2 and 3.
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Figure 6.
Figure 6 Comparison of the IL-17F surface and the TrkA-binding
site on NGF. (A and B) The molecular surface of IL-17F is
oriented as in Figure 5. IL-17F is colored according to the
electrostatic surface potential: red, -5 kT; white, 0 kT; and
blue, +5 kT. The positions of the cavities are indicated by the
circles. (C) The molecular surface of NGF is shown in the same
orientation as IL-17F in (B) with the two protomers of the dimer
colored red and blue; domain 5 of TrkA is shown as a green
ribbon (Wiesmann et al., 1999).
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2001,
20,
5332-5341)
copyright 2001.
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