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PDBsum entry 4z5r
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Cytokine/immune system
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PDB id
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4z5r
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Contents |
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(+ 2 more)
141 a.a.
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(+ 1 more)
217 a.a.
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(+ 1 more)
213 a.a.
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110 a.a.
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117 a.a.
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References listed in PDB file
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Key reference
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Title
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Structural basis of the broadly neutralizing anti-Interferon-α Antibody rontalizumab.
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Authors
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B.Maurer,
I.Bosanac,
S.Shia,
M.Kwong,
R.Corpuz,
R.Vandlen,
K.Schmidt,
C.Eigenbrot.
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Ref.
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Protein Sci, 2015,
24,
1440-1450.
[DOI no: ]
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PubMed id
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Abstract
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Interferons-alpha (IFN-α) are the expressed gene products comprising thirteen
type I interferons with protein pairwise sequence similarities in the 77-96%
range. Three other widely expressed human type I interferons, IFN-β, IFN-κ and
IFN-ω have sequences 29-33%, 29-32% and 56-60% similar to the IFN-αs,
respectively. Type I interferons act on immune cells by producing subtly
different immune-modulatory effects upon binding to the extracellular domains of
a heterodimeric cell-surface receptor composed of IFNAR1 and IFNAR2, most
notably anti-viral effects. IFN-α has been used to treat infection by
hepatitis-virus type C (HCV) and a correlation between hyperactivity of
IFN-α-induced signaling and systemic lupus erythematosis (SLE), or lupus, has
been noted. Anti-IFN-α antibodies including rontalizumab have been under
clinical study for the treatment of lupus. To better understand the rontalizumab
mechanism of action and specificity, we determined the X-ray crystal structure
of the Fab fragment of rontalizumab bound to human IFN-α2 at 3Å resolution and
find substantial overlap of the antibody and IFNA2 epitopes on IFN-α2.
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