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| {{STRUCTURE_2psm| PDB=2psm | SCENE= }} | | {{STRUCTURE_2psm| PDB=2psm | SCENE= }} |
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| '''Crystal structure of Interleukin 15 in complex with Interleukin 15 receptor alpha'''
| | ===Crystal structure of Interleukin 15 in complex with Interleukin 15 receptor alpha=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17947230}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17947230 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17947230}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Sushi]] | | [[Category: Sushi]] |
| [[Category: Transmembrane]] | | [[Category: Transmembrane]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 13:44:05 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 15:22:00 2008'' |
