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PDBsum entry 3di2
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Cytokine/cytokine receptor
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PDB id
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3di2
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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 and biophysical studies of the human il-7/il-7ralpha complex.
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Authors
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C.A.Mcelroy,
J.A.Dohm,
S.T.Walsh.
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Ref.
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Structure, 2009,
17,
54-65.
[DOI no: ]
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PubMed id
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Abstract
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IL-7 and IL-7Ralpha bind the gamma(c) receptor, forming a complex crucial to
several signaling cascades leading to the development and homeostasis of T and B
cells. We report that the IL-7Ralpha ectodomain uses glycosylation to modulate
its binding constants to IL-7, unlike the other receptors in the gamma(c)
family. IL-7 binds glycosylated IL-7Ralpha 300-fold more tightly than
unglycosylated IL-7Ralpha, and the enhanced affinity is attributed primarily to
an accelerated on rate. Structural comparison of IL-7 in complex to both forms
of IL-7Ralpha reveals that glycosylation does not participate directly in the
binding interface. The SCID mutations of IL-7Ralpha locate outside the binding
interface with IL-7, suggesting that the expressed mutations cause protein
folding defects in IL-7Ralpha. The IL-7/IL-7Ralpha structures provide a window
into the molecular recognition events of the IL-7 signaling cascade and provide
sites to target for designing new therapeutics to treat IL-7-related diseases.
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Figure 1.
Figure 1. Binding Kinetic Sensorgrams for the IL-7/IL-7Rα
Interaction Determined Using SPR
(A) Binding kinetics
between unglycosylated IL-7 and IL-7Rα, both from E. coli (EC).
(B and C) Binding kinetics of IL-7 (EC) to glycosylated
IL-7Rα from Chinese hamster ovary (CHO) and Schneider (S2)
insect cells, respectively.
(D) Binding kinetics of IL-7 to
PNGase F-treated IL-7Rα (S2).
(E) Binding kinetics between
IL-7 (EC) and Endo H-treated IL-7Rα (S2).
The binding
kinetics sensorgrams are in black. The red curves are global
fits of the SPR data to a two-step binding reaction model to
determine the binding kinetics.
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Figure 3.
Figure 3. Structural Comparison between Unglycosylated and
Glycosylated IL-7/IL-7Rα Complexes
(A) Superimposition of
the unglycosylated structures (wheat and blue) onto the
glycosylated structure (green) using the D1 and D2 domains of
the receptors.
(B) Molecular surface view of IL-7 and
IL-7Rα highlighting the hydrophobic (orange) and hydrophilic
(lime green) residues in the binding interface.
(C and D)
Bar graphs showing the amount of buried surface area for IL-7
(C) and IL-7Rα (D) in the unglycosylated (red bars) and
glycosylated (blue bars) complexes. Secondary structure
locations are labeled below the residues.
(E) Two views of
the intermolecular interactions observed between the
IL-7/IL-7Rα unglycosylated (wheat) and glycosylated (green)
structures. H bonds are depicted as dashes colored black and
green for the unglycosylated and glycosylated complexes,
respectively.
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The above figures are
reprinted
from an Open Access publication published by Cell Press:
Structure
(2009,
17,
54-65)
copyright 2009.
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