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PDBsum entry 1lk3
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Immune system
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PDB id
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1lk3
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Contents |
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136 a.a.
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210 a.a.
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219 a.a.
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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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Noncompetitive antibody neutralization of il-10 revealed by protein engineering and X-Ray crystallography.
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Authors
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K.Josephson,
B.C.Jones,
L.J.Walter,
R.Digiacomo,
S.R.Indelicato,
M.R.Walter.
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Ref.
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Structure, 2002,
10,
981-987.
[DOI no: ]
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PubMed id
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Abstract
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IL-10 is a dimeric cytokine that must engage its high-affinity cell surface
receptor, IL-10R1, to induce multiple cellular activities. Here we report the
1.9 A crystal structure of an engineered IL-10 monomer (IL-10M1) in complex with
a neutralizing Fab fragment (9D7Fab). 9D7Fab and IL-10R1 bind distinct
nonoverlapping surfaces on IL-10M1. Antagonism of the IL-10M1/IL-10R1
interaction is the result of 9D7Fab-induced conformational changes in the CD
loop of IL-10M1 that indirectly alter the structure of the IL-10R1 binding site.
A single mutation (Ile87Ala) in the same CD loop region of the Epstein-Barr
virus IL-10 (ebvIL-10) also reduces IL-10R1 binding affinity, suggesting that
ebvIL-10 and 9D7Fab use similar allosteric mechanisms to modulate IL-10R1
affinity and biological activity.
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Figure 1.
Figure 1. The IL-10M1/9D7Fab Complex and Interface(A)
Ribbon diagram of the IL-10M1/9D7Fab complex with IL-10M1 in
orange and the 9D7Fab heavy and light chains in red and blue,
respectively. The 9D7Fab epitope, residues 71-83 and 125-137, is
in green.(B) Stereo diagram of the IL-10M1/9D7Fab interface
colored as described in panel A. Nitrogen atoms, blue; oxygen
atoms, red; interfacial waters, magenta spheres; hydrogen bonds,
dashed black lines.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2002,
10,
981-987)
copyright 2002.
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Secondary reference #1
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Title
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Design and analysis of an engineered human interleukin-10 monomer.
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Authors
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K.Josephson,
R.Digiacomo,
S.R.Indelicato,
A.H.Iyo,
T.L.Nagabhushan,
M.H.Parker,
M.R.Walter,
A.H.Ayo.
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Ref.
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J Biol Chem, 2000,
275,
13552-13557.
[DOI no: ]
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PubMed id
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Figure 1.
Fig. 1. Design of an IL-10 monomer. A, schematic diagram
of the IL-10 polypeptide. Each  -helix in
the chain is represented as a rectangle and labeled A-F from the
N to C terminus. The amino acid sequence for the hinge region
between helices D and E is shown for wtIL-10 and for IL-10M1. B,
ribbon diagram of the intertwined wtIL-10 dimer (34). C, ribbon
diagram of a single wtIL-10 chain or open monomer as described
in Ref. 24. D, predicted structure of IL-10M1 showing the
insertion of helices E and F into the cleft formed from helices
A-D.
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Figure 4.
Fig. 4. Thermal denaturation of IL-10M1 and wtIL-10. The
ellipticity at 222 nm for IL-10M1 ( gray trace) and wtIL-10
(black trace) were monitored over the temperature range of 10-95
°C. The protein concentration for the experiment was 40
µg/ml in 20 mM phosphate buffer, pH 7.0.
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The above figures are
reproduced from the cited reference
with permission from the ASBMB
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