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PDBsum entry 3bpo
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Cytokine/cytokine receptor
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PDB id
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3bpo
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Contents |
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98 a.a.
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198 a.a.
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286 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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Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system.
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Authors
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S.L.Laporte,
Z.S.Juo,
J.Vaclavikova,
L.A.Colf,
X.Qi,
N.M.Heller,
A.D.Keegan,
K.C.Garcia.
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Ref.
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Cell, 2008,
132,
259-272.
[DOI no: ]
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PubMed id
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Abstract
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Interleukin-4 and Interleukin-13 are cytokines critical to the development of T
cell-mediated humoral immune responses, which are associated with allergy and
asthma, and exert their actions through three different combinations of shared
receptors. Here we present the crystal structures of the complete set of type I
(IL-4R alpha/gamma(c)/IL-4) and type II (IL-4R alpha/IL-13R alpha1/IL-4, IL-4R
alpha/IL-13R alpha1/IL-13) ternary signaling complexes. The type I complex
reveals a structural basis for gamma(c)'s ability to recognize six different
gamma(c)-cytokines. The two type II complexes utilize an unusual top-mounted
Ig-like domain on IL-13R alpha1 for a novel mode of cytokine engagement that
contributes to a reversal in the IL-4 versus IL-13 ternary complex assembly
sequences, which are mediated through substantially different recognition
chemistries. We also show that the type II receptor heterodimer signals with
different potencies in response to IL-4 versus IL-13 and suggest that the
extracellular cytokine-receptor interactions are modulating intracellular
membrane-proximal signaling events.
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Figure 1.
Figure 1. Structures of the Type I IL-4, Type II IL-4, and
Type II IL-13 Ternary Complexes
(A) The type I complex with
IL-4Rα (blue), IL-4 (red), and γ[c] (gold).
(B) The type
II IL-4 complex with IL-4Rα (blue), IL-4 (red), and IL-13Rα1
(green).
(C) The type II IL-13 complex with IL-4Rα (blue),
IL-13 (yellow-orange), and IL-13Rα1 (green).
The complexes
are shown from the side with a cartoon of a membrane underneath
(left), and as viewed from the “top” (right). Glycan
moieties on Asn residues are shown in ball-and-stick
representation. All figures were generated with PyMol (DeLano,
2002).
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Figure 2.
Figure 2. Structural Similarity between IL-2Rα and IL-13Rα1
Cytokine Engagement
(A) The quaternary complex of IL-2
(pink), IL-2Rα (cyan), IL-2Rβ (blue), and γ[c] (gold).
IL-2Rα is bound to the top surface of IL-2.
(B) Ternary
complex of IL-13 (yellow-orange), IL-4Rα (blue), and IL-13Rα1
(green).
(C) As viewed from the top, the overlapping
cytokine binding sites by IL-2Rα and IL-13Rα1 D1 domains are
apparent. Semitransparent ovals have been drawn around the D1
domain of IL-2Rα and IL-13Rα1 so that regions of overlap are
clear.
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The above figures are
reprinted
from an Open Access publication published by Cell Press:
Cell
(2008,
132,
259-272)
copyright 2008.
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