3bpo
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= IL13 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), IL4R, 582J2.1, IL4RA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), IL13RA1, IL13R, IL13RA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= IL13 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), IL4R, 582J2.1, IL4RA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), IL13RA1, IL13R, IL13RA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[3bpl|3BPL]], [[3bpn|3BPN]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bpo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bpo OCA], [http://www.ebi.ac.uk/pdbsum/3bpo PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3bpo RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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-4Ralpha/gamma(c)/IL-4) and type II (IL-4Ralpha/IL-13Ralpha1/IL-4, IL-4Ralpha/IL-13Ralpha1/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-13Ralpha1 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. | 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-4Ralpha/gamma(c)/IL-4) and type II (IL-4Ralpha/IL-13Ralpha1/IL-4, IL-4Ralpha/IL-13Ralpha1/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-13Ralpha1 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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| + | ==Disease== | ||
| + | Known disease associated with this structure: Allergic rhinitis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147683 147683]], Asthma, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147683 147683]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Garcia, K C.]] | [[Category: Garcia, K C.]] | ||
| - | [[Category: NAG]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
[[Category: cytokine]] | [[Category: cytokine]] | ||
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[[Category: transmembrane]] | [[Category: transmembrane]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:28:05 2008'' |
Revision as of 02:28, 31 March 2008
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| , resolution 3.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | and | ||||||
| Ligands: | |||||||
| Gene: | IL13 (Homo sapiens), IL4R, 582J2.1, IL4RA (Homo sapiens), IL13RA1, IL13R, IL13RA (Homo sapiens) | ||||||
| Related: | 3BPL, 3BPN
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the IL13-IL4R-IL13Ra ternary complex
Contents |
Overview
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-4Ralpha/gamma(c)/IL-4) and type II (IL-4Ralpha/IL-13Ralpha1/IL-4, IL-4Ralpha/IL-13Ralpha1/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-13Ralpha1 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.
Disease
Known disease associated with this structure: Allergic rhinitis, susceptibility to OMIM:[147683], Asthma, susceptibility to OMIM:[147683]
About this Structure
3BPO is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Molecular and Structural Basis of Cytokine Receptor Pleiotropy in the Interleukin-4/13 System., Laporte SL, Juo ZS, Vaclavikova J, Colf LA, Qi X, Heller NM, Keegan AD, Garcia KC, Cell. 2008 Jan 25;132(2):259-272. PMID:18243101
Page seeded by OCA on Mon Mar 31 05:28:05 2008
