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2psm
From Proteopedia
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| 2psm, resolution 2.19Å () | |||||||||
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| Ligands: | |||||||||
| Gene: | Il15 (Mus musculus), Il15ra (Mus musculus) | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB, TOPSAN | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
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. 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 Sun May 4 13:44:05 2008
Categories: 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. | Alternative splicing | Cytokine | Endoplasmic reticulum | Glycoprotein | Golgi apparatus | Membrane | National project on protein structural and functional analyse | Nppsfa | Nucleus | Phosphorylation | Receptor | Riken structural genomics/proteomics initiative | Rsgi | Secreted | Structural genomic | Sushi | Transmembrane
