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Immune system
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PDB id
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1md6
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Contents |
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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Cellular component
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cellular_component
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3 terms
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Biological process
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biological_process
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2 terms
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Biochemical function
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molecular_function
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3 terms
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DOI no:
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Biochemistry
42:10938-10944
(2003)
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PubMed id:
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High-resolution structure of murine interleukin 1 homologue IL-1F5 reveals unique loop conformations for receptor binding specificity.
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E.F.Dunn,
N.J.Gay,
A.F.Bristow,
D.P.Gearing,
L.A.O'Neill,
X.Y.Pei.
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ABSTRACT
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Interleukin-1 (IL-1) F5 is a novel member of the IL-1 family. The IL-1 family
are involved in innate immune responses to infection and injury. These cytokines
bind to specific receptors and cause activation of NFkappaB and MAP kinase.
IL-1F5 has a sequence identity of 44% to IL-1 receptor antagonist (IL-1Ra), a
natural antagonist of the IL-1 system. Here we report the crystal structure of
IL-1F5 to a resolution of 1.6 A. It has the same beta-trefoil fold as other IL-1
family members, and the hydrophobic core is well conserved. However, there are
substantial differences in the loop conformations, structures that confer
binding specificity for the cognate receptor to IL-1beta and the antagonist
IL-1Ra. Docking and superimposition of the IL-1F5 structure suggest that is
unlikely to bind to the interleukin1 receptor, consistent with biochemical
studies. The structure IL-1F5 lacks features that confer antagonist properties
on IL-1Ra, and we predict that like IL-1beta it will act as an agonist. These
studies give insights into how distinct receptor specificities can evolve within
related cytokine families.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.E.Sims,
and
D.E.Smith
(2010).
The IL-1 family: regulators of immunity.
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Nat Rev Immunol, 10,
89.
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A.Lingel,
T.M.Weiss,
M.Niebuhr,
B.Pan,
B.A.Appleton,
C.Wiesmann,
J.F.Bazan,
and
W.J.Fairbrother
(2009).
Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors--insight into heterotrimeric IL-1 signaling complexes.
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Structure, 17,
1398-1410.
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PDB code:
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C.Costelloe,
M.Watson,
A.Murphy,
K.McQuillan,
C.Loscher,
M.E.Armstrong,
C.Garlanda,
A.Mantovani,
L.A.O'Neill,
K.H.Mills,
and
M.A.Lynch
(2008).
IL-1F5 mediates anti-inflammatory activity in the brain through induction of IL-4 following interaction with SIGIRR/TIR8.
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J Neurochem, 105,
1960-1969.
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S.Gosavi,
P.C.Whitford,
P.A.Jennings,
and
J.N.Onuchic
(2008).
Extracting function from a beta-trefoil folding motif.
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Proc Natl Acad Sci U S A, 105,
10384-10389.
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D.Magne,
G.Palmer,
J.L.Barton,
F.Mézin,
D.Talabot-Ayer,
S.Bas,
T.Duffy,
M.Noger,
P.A.Guerne,
M.J.Nicklin,
and
C.Gabay
(2006).
The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes.
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Arthritis Res Ther, 8,
R80.
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J.E.Towne,
K.E.Garka,
B.R.Renshaw,
G.D.Virca,
and
J.E.Sims
(2004).
Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs.
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J Biol Chem, 279,
13677-13688.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
