2psm: Difference between revisions
New page: left|200px<br /><applet load="2psm" size="350" color="white" frame="true" align="right" spinBox="true" caption="2psm, resolution 2.19Å" /> '''Crystal structure of... |
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==Overview== | ==Overview== | ||
Interleukin (IL)-15 is a pleiotropic cytokine that plays a pivotal role in | Interleukin (IL)-15 is a pleiotropic cytokine that plays a pivotal role in both innate and adaptive immunity. IL-15 is unique among cytokines due to its participation in a trans signaling mechanism in which IL-15 receptor alpha (IL-15Ralpha) from one subset of cells presents IL-15 to neighboring IL-2Rbeta/gammac-expressing cells. Here we present the crystal structure of IL-15 in complex with the sushi domain of IL-15Ralpha. The structure reveals that the alpha receptor-binding epitope of IL-15 adopts a unique conformation, which, together with amino acid substitutions, permits specific interactions with IL-15Ralpha that account for the exceptionally high affinity of the IL-15.IL-15Ralpha complex. Interestingly, analysis of the topology of IL-15 and IL-15Ralpha at the IL-15.IL-15Ralpha interface suggests that IL-15 should be capable of participating in a cis signaling mechanism similar to that of the related cytokine IL-2. Indeed, we present biochemical data demonstrating that IL-15 is capable of efficiently signaling in cis through IL-15Ralpha and IL-2Rbeta/gammac expressed on the surface of a single cell. Based on our data we propose that cis presentation of IL-15 may be important in certain biological contexts and that flexibility of IL-15Ralpha permits IL-15 and its three receptor components to be assembled identically at the ligand-receptor interface whether IL-15 is presented in cis or trans. Finally, we have gained insights into IL-15.IL-15Ralpha.IL-2Rbeta.gammac quaternary complex assembly through the use of molecular modeling. | ||
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
Crystal | Crystal Structure of the interleukin-15.interleukin-15 receptor alpha complex: insights into trans and cis presentation., Olsen SK, Ota N, Kishishita S, Kukimoto-Niino M, Murayama K, Uchiyama H, Toyama M, Terada T, Shirouzu M, Kanagawa O, Yokoyama S, J Biol Chem. 2007 Dec 21;282(51):37191-204. Epub 2007 Oct 18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17947230 17947230] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: Kukimoto-Niino, M.]] | [[Category: Kukimoto-Niino, M.]] | ||
[[Category: Murayama, K.]] | [[Category: Murayama, K.]] | ||
[[Category: Olsen, S | [[Category: Olsen, S K.]] | ||
[[Category: Ota, N.]] | [[Category: Ota, N.]] | ||
[[Category: RSGI, RIKEN | [[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]] | ||
[[Category: Shirouzu, M.]] | [[Category: Shirouzu, M.]] | ||
[[Category: Terada, T.]] | [[Category: Terada, T.]] | ||
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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 Thu Feb 21 18:32:40 2008'' | ||
Revision as of 16:32, 21 February 2008
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Crystal structure of Interleukin 15 in complex with Interleukin 15 receptor alpha
Overview
Interleukin (IL)-15 is a pleiotropic cytokine that plays a pivotal role in both innate and adaptive immunity. IL-15 is unique among cytokines due to its participation in a trans signaling mechanism in which IL-15 receptor alpha (IL-15Ralpha) from one subset of cells presents IL-15 to neighboring IL-2Rbeta/gammac-expressing cells. Here we present the crystal structure of IL-15 in complex with the sushi domain of IL-15Ralpha. The structure reveals that the alpha receptor-binding epitope of IL-15 adopts a unique conformation, which, together with amino acid substitutions, permits specific interactions with IL-15Ralpha that account for the exceptionally high affinity of the IL-15.IL-15Ralpha complex. Interestingly, analysis of the topology of IL-15 and IL-15Ralpha at the IL-15.IL-15Ralpha interface suggests that IL-15 should be capable of participating in a cis signaling mechanism similar to that of the related cytokine IL-2. Indeed, we present biochemical data demonstrating that IL-15 is capable of efficiently signaling in cis through IL-15Ralpha and IL-2Rbeta/gammac expressed on the surface of a single cell. Based on our data we propose that cis presentation of IL-15 may be important in certain biological contexts and that flexibility of IL-15Ralpha permits IL-15 and its three receptor components to be assembled identically at the ligand-receptor interface whether IL-15 is presented in cis or trans. Finally, we have gained insights into IL-15.IL-15Ralpha.IL-2Rbeta.gammac quaternary complex assembly through the use of molecular modeling.
About this Structure
2PSM is a Protein complex structure of sequences from Mus musculus with BAM as ligand. Full crystallographic information is available from OCA.
Reference
Crystal Structure of the interleukin-15.interleukin-15 receptor alpha complex: insights into trans and cis presentation., Olsen SK, Ota N, Kishishita S, Kukimoto-Niino M, Murayama K, Uchiyama H, Toyama M, Terada T, Shirouzu M, Kanagawa O, Yokoyama S, J Biol Chem. 2007 Dec 21;282(51):37191-204. Epub 2007 Oct 18. PMID:17947230
Page seeded by OCA on Thu Feb 21 18:32:40 2008
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Mus musculus
- Protein complex
- Kanagawa, O.
- Kishishita, S.
- Kukimoto-Niino, M.
- Murayama, K.
- Olsen, S K.
- Ota, N.
- RSGI, RIKEN Structural Genomics/Proteomics Initiative.
- Shirouzu, M.
- Terada, T.
- Yokoyama, S.
- BAM
- Alternative splicing
- Cytokine
- Endoplasmic reticulum
- Glycoprotein
- Golgi apparatus
- Membrane
- National project on protein structural and functional analyses
- Nppsfa
- Nucleus
- Phosphorylation
- Receptor
- Riken structural genomics/proteomics initiative
- Rsgi
- Secreted
- Structural genomics
- Sushi
- Transmembrane
