3bpn: Difference between revisions
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caption="3bpn, resolution 3.02Å" /> | caption="3bpn, resolution 3.02Å" /> | ||
'''Crystal structure of the IL4-IL4R-IL13Ra ternary complex'''<br /> | '''Crystal structure of the IL4-IL4R-IL13Ra ternary complex'''<br /> | ||
==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. | |||
==About this Structure== | ==About this Structure== | ||
3BPN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=AC1:Nag+Binding+Site+For+Residue+B+901'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BPN OCA]. | 3BPN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=AC1:Nag+Binding+Site+For+Residue+B+901'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BPN 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18243101 18243101] | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Garcia, K | [[Category: Garcia, K C.]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
Line 27: | Line 33: | ||
[[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 Thu Feb 21 19:06:54 2008'' |
Revision as of 20:06, 21 February 2008
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Crystal structure of the IL4-IL4R-IL13Ra ternary complex
OverviewOverview
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.
About this StructureAbout this Structure
3BPN is a Protein complex structure of sequences from Homo sapiens with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
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
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