2psm

Crystal structure of Interleukin 15 in complex with Interleukin 15 receptor alpha

spinqualitylabelsall models 2psm, resolution 2.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2psm is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BAM Gene: Il15 (Mus musculus), Il15ra (Mus musculus) Resources: FirstGlance, OCA, RCSB, PDBsum, TOPSAN Function [IL15_MOUSE] Cytokine that stimulates the proliferation of T-lymphocytes. Stimulation by IL-15 requires interaction of IL-15 with components of IL-2R, including IL-2R beta and probably IL-2R gamma but not IL-2R alpha. [I15RA_MOUSE] High-affinity receptor for interleukin-15. Can signal both in cis and trans where IL15R from one subset of cells presents IL15 to neighboring IL2RG-expressing cells. Signal transduction seems to involve STAT3, STAT5, STAT6, JAK2 and SYK. Expression of different isoforms may alter or interfere with signal transduction. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Interleukin Interleukin receptor

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