2psm | pdb_00002psm

File:2psm.jpg

spinqualitylabelsall models 2psm, resolution 2.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D

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-15Ralpha from, one subset of cells presents IL-15 to neighboring IL-2Rbeta/gamma(c), 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, permit 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 suggest 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/gamma(c) 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/gamma(c) 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 Oct 18;. PMID:17947230

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